key: cord-0928500-mzpld6do
authors: Sahu, Utkarsha; Biswas, Debasis; Prajapati, Vijay Kumar; Singh, Anirudh K.; Samant, Mukesh; Khare, Prashant
title: Interleukin‐17—A multifaceted cytokine in viral infections
date: 2021-06-16
journal: J Cell Physiol
DOI: 10.1002/jcp.30471
sha: 5c89010932d0d6e2507b218dccdb44aa7da27d2f
doc_id: 928500
cord_uid: mzpld6do

Viral infections are a major threat to the human population due to the lack of selective therapeutic measures. The morbidity and mortality reported worldwide are very alarming against viral pathogens. The proinflammatory environment is required for viral inhibition by initiating the host immune response. The host immune response fights these pathogens by secreting different cytokines. Interleukin‐17 (IL‐17) a proinflammatory cytokine mainly produced by T helper type 17 cells, plays a vital role in the regulation of host immune response against various pathogens, including viruses. However, dysregulated production of IL‐17 induces chronic inflammation, autoimmune disorders, and may lead to cancer. Recent studies suggest that IL‐17 is not only involved in the antiviral immune response but also promotes virus‐mediated illnesses. In this review, we discuss the protective and pathogenic role of IL‐17 against various viral infections. A detailed understanding of IL‐17 during viral infections could contribute to improve therapeutic measures and enable the development of an efficient and safe IL‐17 based immunotherapy.

Viral infections can cause acute and chronic pathological responses, which lead to high rates of mortality and morbidity. Their pathology is dependent on the type and nature of the virus as well as the infected organ of the human body ( Figure 1 ). Different human viruses have unique pathologies and modes of infection. For instance, respiratory syncytial virus (RSV) and influenza viruses primarily infect the respiratory system and may cause respiratory failure. Coronaviruses (CoVs), such as severe acute respiratory syndrome virus (SARS), Middle East respiratory syndrome virus (MERS), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are associated with lung pathology and acute respiratory distress syndrome (ARDS) (Pal et al., 2020) . Hepatitis B virus (HBV) and hepatitis C virus (HCV) attack hepatic cells, where persistent infection along with chronic liver inflammation can lead to complications such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) (Bray et al., 2018) . Human papillomavirus (HPV) targets the epithelial layer of the genital tract creating lesions and may lead to cervical cancer (Blaskewicz et al., 2011) . Severe dengue virus (DENV) infection affects kidneys, lungs and liver (Póvoa et al., 2014) . Human immunodeficiency virus (HIV) mainly targets the host T-lymphocytes. The current prophylactic and therapeutic strategies are very limited against viral infections.

In case of HPV, so far we could be able to develop only three vaccines that are currently being used (https://www.who.int/teams/immunizationvaccines-and-biologicals/diseases/human-papillomavirus-vaccines-(HPV).

Similarly there are different vaccines under clinical trials against SARS-CoV-2 (Rawat et al., 2021) while on the therapeutic point of view, different antiviral drugs against HBV (de Clercq et al., 2010) , HCV (Feeney & Chung, 2014; Pol et al., 2013) , RSV (Empey et al., 2010) , herpes simplex virus (HSV) (Hook & Friedman, 2007) and influenza (Allen et al., 2006) are being given to patients. However, there are several viral infections like HIV/Simian immunodeficiency virus (SIV), dengue, Zika virus (ZIKV), and coxsackievirus B3 (CVB3) with no effective antivirals.

The development of viral infection needs to win over both innate and adaptive immune responses (Braciale et al., 2012) . Upon viral infection, the viral elements including nucleic acids and other pathogen associated molecular patterns are recognized by different pathogen recognition receptors such as toll like receptors, NOD like receptors, and RIG like receptors. This initiates a cascade of downstream signaling triggering the innate immune response. Entry of virus into the host activates innate immune cells such as macrophage cells, dendritic and granulocytes within a few hours at the site of infection which subsequently activates highly specific adaptive immune response mediated by lymphocytes (B & T cells) (Koyama et al., 2008) . Development of specific adaptive immune response against various infections requires 1-2 weeks. A strong inflammatory response is required for viral clearance and control; however, the severity of inflammation has to be tightly regulated to avoid tissue damage and adverse pathogenesis.

IL-17 is a principal proinflammatory cytokine that plays an important role in producing a protective immune response along with other inflammatory cytokines. IL-17 also known as cytotoxic T-lymphocyteassociated protein 8 (CTLA-8), was discovered by Rouvier et al. (1993) .

Recently, it has emerged as a crucial factor in the host immune response and is produced by multiple cell types, including T helper type 17 (Th17) (Park et al., 2005) , gamma delta T (γδT) (G. Kim et al., 2018) , Type 17 CD8 + T (Tc17) (Huber et al., 2013) , and natural killer (NK) cells (Passos et al., 2010) . The differentiation of mouse Th17 cells requires IL-1β, IL-6, IL-23, and transforming growth factor beta (TGF-β). However, the human Th17 cell differentiation is independent of TGF-β (Miossec & Kolls, 2012) .

The lineage-specific transcription factor retinoic acid receptor-related orphan receptor-γt (ROR-γt) and signal transducer and activator of transcription 3 (STAT3) are important players for Th17 cell differentiation (Miossec & Kolls, 2012) . The IL-17 family has 6 members including IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F. Among them, IL-17A is the most explored member of the family and is also known as IL-17 (Brevi et al., 2020; McGeachy et al., 2019) .

The IL-17 receptor family consists of five members: IL-17RA, IL-17RB, IL-17RC, IL-17RD, and IL-17RE which are single-pass transmembrane receptors with conserved domains (Brevi et al., 2020) . IL-17 targets different cells such as endothelial cells, epithelial cells, macrophages and dendritic cells (S. Xu & Cao, 2010) . After binding of IL-17 with its receptor IL-17RA, an adapter protein ACT1 recruits to the similar expression to fibroblast growth factor genes (SEF) and IL-17R (SEFIR) cytoplasmic domain of the receptor followed by TGF-βactivated kinase 1 (TAK1) and tumor necrosis factor (TNF)-receptor associated factor 6 (TRAF6) ubiquitin ligase. Recruitment and ubiquitination of TRAF6 activate transcription factor Nuclear factor kappa B (NF-κB) pathway (Brevi et al., 2020; Qian et al., 2007) . IL-17 induces secretion of granulocyte colony-stimulating factor (GCSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), as well as various chemokine ligands such as, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X-C motif) ligand 2 (CXCL2) and chemokine (C-X-C motif) ligand 8 (CXCL8). The inflammatory response produced by IL-17 triggers the migration and accumulation of neutrophils at the site of infection (Gaffen, 2009 ). IL-17 plays a crucial role to protect from microbial infections (Veldhoen, 2017) . In viral infections, it shows both protective and pathogenic roles in infected cells (Figure 2 ).

Host single nucleotide polymorphisms (SNPs) in various genes also modulate viral diseases in humans. SNP is a substitution of a single F I G U R E 1 Association of interleukin-17 (IL-17) with various viruses and their target organs in the human body nucleotide by another at a specific position in the genome. IL-17 gene has different SNPs, closely associated with many human diseases, autoimmune disorders and cancer (Blauvelt & Chiricozzi, 2018; Z. M. Dai et al., 2016; Keshavarz et al, 2019) . SNPs −737C>T (rs8193036) and −197G>A (rs2275913) in the IL-17A promoter and the SNP 7488T>C (rs763780) in exon 3 of IL-17F (Ren et al., 2017) are associated with viral persistence and pathology; however, the mechanism remains unexplored. The proinflammatory properties of IL-17 make it a key mediator of inflammation and immunopathology (S. Chen et al., 2019) .

Here, we have extensively explored the multifaceted role of IL-17 and its involvement against major viral infections (Table 1) Doorslaer et al., 2018) . It is mainly associated with female genital tract infections causing cervical lesions and cancer. HPV has evolved several mechanisms to evade host immune response and establish a local immunosuppressive environment by downregulating the cytokine production and facilitating persistent viral infection. The uterine cervix epithelium seems to be hyperresponsive towards HPV infection (Blaskewicz et al., 2011; Tran et al., 2015) . Th17 cells and IL-17A mediate immune augmentation in the high-risk HPV infection, especially in the cervical microenvironment leading to disease progression (Park et al., 2005; Xue et al., 2018) . The analysis of Th17 cell percentages of patients with different grade cervical interepithelial neoplasia (CIN) revealed a gradual increase in Th17 cells during the progression of cervical lesions (Xue et al., 2018) . The host immune system deviating environment induced by HPV can be overcome by the use of 2,4-dinitrochlorobenzene (DNCB). In keratinocytes expressing HPV16 E7 oncogenic protein, the DNCB treatment stimulated a hyperinflammatory environment via IL-17A mediated arginase-1 production which is responsible for viral clearance. The blockage of IL-17A or arginase-1 inhibited hyperinflammatory response in DNCB treated cells. This suggests an active involvement of IL-17A in DNCB mediated hyperinflammatory response against HPV16 E7 expressing cells (Blaskewicz et al., 2011; Tran et al., 2015) .

T-cell-mediated immune responses against HPV are believed to play a significant role in cervical carcinogenesis (Blaskewicz et al., 2011) .

F I G U R E 2 Protective and pathogenic role of interleukin-17 (IL-17). (a) Normal condition: The different subsets of IL-17 producing cells secrete basal level of IL-17 that is crucial for maintaining tissue integrity. (b) Postinfection condition: (i) Protective role-The IL-17 producing cells get differentiated/ activated after viral infection and start secreting IL-17 that triggers the recruitment of neutrophils and macrophages by secreting different chemokinesand activates the adaptive immune response for viral clearance. (ii) Pathogenic role-Upon viral infection, the dysregulated IL-17 production leads to hyperinflammation causing elevated Muc5ac expression which leads to increased mucus secretion, it also reduces the expression of viral inhibitory RNAse which favors the viral persistence. Hyperinflammation induced by IL-17 also cause the release of matrix metalloproteinase and oxyradicals which leads to disruption of tissue integrity, further it upregulates the antiapoptotic molecules and finally leads to cancer T A B L E 1 Pathogenic and protective involvement of IL-17 with SNPs in viral infections Chang et al., 2010; Cong et al., 2015; Gosmann et al., 2014; Park et al., 2005; Vidal et al., 2015; Xue et al., 2018; N. Zhang et al., 2016) RNA viruses

Pathogenic role • Involved in CVB3 induced AVMC pathology and pancreatitis • Upregulated mRNA and protein levels of IL-17 promotes viral replication • CVB3 induces Th17 cell differentiation • The reduced IL-17 levels after nicotine treatment reduced disease severity • The reduced expression of IL-17 after Fasudil treatment reduced myocardial lesions, viral replication and increased survival in CVB3 infected hearts in murine model (K. Dai et al., 2018; Kong et al., 2013; Li-Sha et al., 2015; Long et al., 2016; F. Yan et al., 2019; Yang et al., 2011; Yuan et al., 2010) CoVs Pathogenic role • Causes ARDS by contributing in the cytokine storm • Lung tissue damage by secretion of matrix metalloproteinases Mahallawi et al., 2018; D. Wu & Yang, 2020) DENV Protective role • Induces the expression of TNF-α mediated proadhesive molecules and GRO-α leading to neutrophil recruitment Pathogenic role • Increased secretion of proinflamatory cytokine IL-1β • High IL-17 levels in children with severe dengue • Increased IL-17 level in respiratory distress and pleural effusion • Promoting the production of proinflammatory cytokines IL-6 and IL-8 which contribute to DHF pathogenesis (Jain et al, 2013; Jovanovic et al., 1998; Moreno-Altamirano et al, 2004; Raghupathy et al., 1998; Restrepo et al., 2008; Witowski et al., 2000) HCV Protective role • Inhibition of Th-17 cells by immunosuppressive cytokines (IL-10 and TGF-β) secreted during HCV Infection Pathogenic role (Faber et al., 2012; Habibi et al., 2020; Hashimoto et al., 2005; X. Hu et al., 2019; Mebratu & Tesfaigzi, 2018; Newcomb et al., 2013; Shi et al., 2017; Stoppelenburg et al., 2013) Retro viruses (Cong et al., 2015; Vidal et al., 2015) . The polymerase chain reactionrestriction fragment length polymorphism results suggested that the individuals with AA and GA genotypes of IL-17A have higher risk of cervical cancer as compared to people with GG genotype (Cong et al., 2015) . IL-17 was found more frequently in cervical cancer samples of women infected with HPV16/18 compared to women infected with other genotypes of HPV (Vidal et al., 2015) . showed a strong association with TNF-α in the recruitment of neutrophils and is thought to be a crucial immune activator in HCF (Maertzdorf et al., 2002) . IL-17A plays an important role in enhancing antiviral T helper Type 1 (Th1) response in the female genital tract (Bagri et al., 2017) . In IL-17A KO mice, the protective immune response against HSV-2 reinfection was impaired and the mice showed increased pathology, viral shedding and mortality as compared to wild type (WT) mice. Furthermore, the absence of IL-17A coincided with deficient interferon gamma (IFN-γ) production (Bagri et al., 2017) . The generation of beta-defensin-3 in response to IL-17A induction by human herpes simplex vaccine VC2 at the vaginal mucosal surface in guinea pigs Cavia porcellus gave protection against HSV-2 infection.

Human vaginal tissues also responded in a similar manner leading to reduced HSV-2 progeny (Stanfield et al., 2018) . The role of HSV in peripheral nerve damage is debated because on one hand IL-17C secreted in response to HSV-2 infection is responsible for peripheral nerve growth (Peng et al., 2017) . On the contrary, IL-17 induces the production of matrix metalloproteinases (MMPs) and oxyradicals like tissue-damaging factors and also acts as a neutrophil survival factor (Suryawanshi et al., 2011) . IL-17C also provided surviving signals to protect neurons during HSV infection (Peng et al, 2017) thereby indicating the dual role of IL-17, that is, both protective and pathogenic effects in host tissues (Figure 1 ). (Dennert et al., 2008) . The current understanding suggests the crucial role of IL-17A and Th17 cells in Fasudil, A Rho kinase inhibitor was also reported to reduce IL-17A expression, myocardial lesions, viral replication and increase survival in CVB3 infected hearts in BALB/c murine model (K. Dai et al., 2018) .

In summary, IL-17 plays pathogenic role after CVB3 infection leading to cardiac injury and blocking of IL-17 reduces disease severity.

CoVs (Jain et al., 2013) . Similar results of elevated IL-17 level in DENV infection was reported by Becquart et al. (Becquart et al., 2010) . A positive association of increased IL-17 level was also reported in respiratory distress and pleural effusion (Jain et al., 2013) . Although the direct role of IL-17 is still under investigation, few reports have shown that IL-17 promoted the production of proinflammatory cytokines IL-6 and IL-8 which contributed to the pathogenesis of DHF (Raghupathy et al., 1998; Restrepo et al., 2008) . IL-17 stimulates the secretion of another proinflammatory cytokine IL-1β, by human macrophages (Friedlander et al., 1996) . 

HCV is an enveloped positive-strand ssRNA virus with about a 9.6 kb genome belonging to the Flaviviridae family. It causes chronic hepatitis, which progresses to liver cirrhosis and HCC (Kato, 2000) . The 1957 -1958 and H3N2 associated with Hong Kong pandemic in 1968 -1969 In addition, the H5N1, H7N9 avian influenza and H9N2 influenza strains possess a high pandemic potential (Shan et al., 2019; Song & Qin, 2020; Taubenberger & Morens, 2010) .

Cytokine dysregulation is associated with severe disease outcomes in influenza infection (https://www.who.int/en/news-room/factsheets/detail/influenza-[seasonal]; Keshavarz et al, 2019) . As compared to seasonal influenza the pandemic H1N1 influenza causes increased extrapulmonary complications and without timely treatment, the mortality risk was increased in pandemic H1N1 infection (N. . In addition, the patients infected with pandemic H1N1 had slower viral clearance in the lower respiratory tract during antiviral treatment (N. . The bacterial superinfection along with pandemic H1N1 infection exacerbates the severity (N. . Seasonal influenza is associated with a strong cytokine response including IL-17, while pandemic H1N1 influenza is known to suppress the immune response (N. . As compared to seasonal influenza, in pandemic H1N1 infection, the Th17 mediated adaptive immune response was suppressed with a decreased IL-17A level. An pathogenesis in infants as well as in BALB/c mouse model of RSV (Mukherjee et al., 2011) . Also, the ratio of Th17 cells and Treg cells is linked with RSV induced pathology (Mangodt et al., 2015) . In an RSV infected C57BL/6 mouse model, the balance of Th17/Treg ratio was related to the pathogenesis of RSV induced bronchiolitis (Mebratu & Tesfaigzi, 2018) . There is less information about IL-17A induced lung injury, but IL-17A level was increased in the bronchial submucosa site in chronic obstructive pulmonary disease, leading to mucus cell emphysema after RSV infection (Ishioka et al., 2013) . RSV infection is a prominent cause of exacerbation of asthma (Ishioka et al., 2013; Sigurs et al., 2005) . The reduced tolerance to asthma is caused by increased IL-17A producing cells in lungs via chemokine receptor 6 (CCR6) and chemokine ligand 20 (CCL20) signaling (Shi et al., 2017) .

IL-17 induces the mucin 5ac (Muc5ac) expression which is directly related to mucus production in the respiratory tract ( Figure 2 ) (Yin Chen et al., 2003) . The elevated level of IL-17 in STAT1 KO mice infected with RSV increased the mucus production and airway distress (Hashimoto et al., 2005) . Apart from increasing the disease severity, a protective role of IL-17A has also been reported in RSV infection (Faber et al., 2012; Newcomb et al., 2013) . (Faber et al., 2012) . In RSV infected BALB/c mice with ovalbumin (OVA)-induced allergic airway inflammation (OVA/RSV), IL-17A level significantly increased after 6 days postinfection. Also, IL-17A KO OVA/RSV mice had increased airway reactivity (AR) as compared with WT OVA/RSV mice, implying a negative correlation between IL-17A and RSV induced AR (Newcomb et al., 2013) . A recent study on RSV infection reported a protective role of IL-17A in viral clearance during early phase of infection (Habibi et al., 2020) . The RSV infection is associated with IL-17 mediated increased mucus production, neutrophil infiltration and bronchiolitis. On the contrary, IL-17 also leads to viral clearance, reduces the AR in RSV infection and promotes disease recovery. T allele of TT genotype at IL-17F 7488T>C are associated with increased risk to HBV infection (Ren et al., 2017) . In addition, the IL-17A −737C>T SNP is also associated with increased HBV persistence . Altogether, these studies suggest an active participation of IL-17 SNPs in HBV infection. Thus it can be concluded that IL-17 is involved in HBV induced hepatic diseases, CHB, acute to chronic liver failure, liver cirrhosis, and HCC due to dysregulation in inflammatory response but also inhibits viral replication that was correlated with secretion of MxA and OAS mRNA. (Miyahara et al., 2008) . Recent reports showed that targeting IL-17 could inhibit disease severity and reduce clinical symptoms (Robinson et al., 2013) . Currently there are three main biologics or neutralizing antibodies that are clinically adopted to block the function of IL-17 namely, ixekizumab, secukinumab and brodalumab. The therapeutic application of these antibodies was well explored against autoimmune disorders like psoriasis, psoriatic arthritis (Iain & Mcinnes, 2016; McInnes et al., 2014) , ankylosing spondylitis (Yin et al., 2020) , rheumatoid arthritis (Genovese et al., 2010) and experimental autoimmune encephalomyelitis (mouse model of multiple sclerosis) (Lock et al., 2002) . ROR-γt is the master transcription factor for IL-17 secretion. Inhibition of ROR-γt has been proposed as a therapeutic target in skin pathologies and Crohn's disease (Bassolas-Molina et al., 2018; Ecoeur et al., 2019) . In addition, STAT3 is also a major transcription factor required for IL-17 production. Inhibition of STAT3 by a small molecule C188-9 significantly reduced the airway inflammation and Th17 accumulation in murine asthma (Gavino et al., 2016) . Recently, it was suggested that targeting the JAK transcription factor by its inhibitor Fedratinib The IL-17 mediated immune response varies in the cell and tissue microenvironment. For example, in lung epithelium, IL-17 signaling induces the secretion of CXCL-5, IL-6, and IL-8, and aids neutrophil recruitment (K. Kawaguchi et al., 2001) . In NK cells, IL-17 induces GM-CSF for the proliferation of Kupffer cells (Wanqiu Hou et al., 2009; W. Hou et al., 2014) . In the intestinal epithelial cells, the IL-17 signaling via ACT1 produces occludin crucial for tissue integrity (J. S. Lee et al., 2015) . In addition, IL-17 induces the secretion of collagen I protein in the liver, thus contributing to liver fibrosis (W. Hou et al., 2014) . Thus the multifaceted functions of IL-17 signaling depending upon the cell and tissue microenvironment make it a crucial factor during viral infections.

In this review, we have tried to address the pathogenic and 

Th17 and IL-17 as predictors of hepatic inflammation in patients with chronic hepatitis C virus infection and treated with direct antiviral therapy

The use of antiviral drugs for influenza: Recommended guidelines for practitioners

Imbalanced pro-and anti-Th17 responses (IL-17/granulocyte colony-stimulating factor) predict fatal outcome in 2009 pandemic influenza

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Th17 serum cytokines in relation to laboratory-confirmed respiratory viral infection: A pilot study

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Novel role for interleukin-17 in enhancing type 1 helper T cell immunity in the female genital tract following mucosal herpes simplex virus 2 vaccination

Decreased frequencies of Th17 and Tc17 cells in patients infected with avian influenza A (H7N9) virus

An RORγt oral inhibitor modulates IL-17 responses in peripheral blood and intestinal mucosa of Crohn's disease patients

Acute dengue virus 2 infection in Gabonese patients is associated with an early innate immune response, including strong interferon alpha production

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza

Structure and function of intercellular junctions in human cervical and vaginal mucosal epithelia

The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis

The biology of influenza viruses

Regulating the adaptive immune response to respiratory virus infection

Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Much more than IL-17A: cytokines of the IL-17 family between microbiota and cancer

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The proportion of different interleukin-17-producing T-cell subsets is associated with liver fibrosis in chronic hepatitis C

Th17 cells are increased with severity of liver inflammation in patients with chronic hepatitis C

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Increased IL-17-producing CD4 + T cells in patients with esophageal cancer

IL-17 receptor signaling in the lung epithelium is required for mucosal chemokine gradients and pulmonary host defense against K. pneumoniae

Zika Virus: Rapid spread in the western hemisphere

Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by regulating interleukin-17A content

p300 promotes differentiation of Th17 cells via positive regulation of the nuclear transcription factor RORγt in acute respiratory distress syndrome

Stimulation of airway mucin gene expression by interleukin (IL)−17 through IL-6 paracrine/autocrine loop

Sublingual immunization with an RSV G glycoprotein fragment primes IL-17-mediated immunopathology upon respiratory syncytial virus infection

Human T h 17 cells lack HIV-inhibitory rnases and are highly permissive to productive hiv infection

Antiviral treatment of chronic hepatitis B virus (HBV) infections. Viruses

Association between interluekin-17 gene polymorphisms and the risk of cervical cancer in a Chinese population

Critical role of IL-17RA in immunopathology of influenza infection

Fasudil exerts a cardio-protective effect on mice with coxsackievirus B3-induced acute viral myocarditis

Role of IL-17A rs2275913 and IL-17F rs763780 polymorphisms in risk of cancer development: An updated meta-analysis

Acute viral myocarditis

Increased IL-17 and/or IFN-γ producing T-cell subsets in gut mucosa of long-term-treated HIV-1-infected women

IL-17 and IL-22 production in HIV+ individuals with latent and active tuberculosis

Direct whole-genome deep-sequencing of human respiratory syncytial virus A and B from Vietnamese children identifies distinct patterns of inter-and intra-host evolution

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Parallel assessment of Th17 cell frequencies by surface marker co-expression versus ex vivo IL-17 production in HIV-1 infection

Antagonizing retinoic acid-related-orphan receptor gamma activity blocks the T Helper 17/Interleukin-17 pathway leading to attenuated pro-inflammatory human keratinocyte and skin responses

IL17A gene polymorphism, serum IL17 and total IgE in Egyptian population with chronic HCV and hepatocellular carcinoma

Possible role of interleukin-17 and macrophage migration inhibitory factor in cutaneous warts

Pharmacologic advances in the treatment and prevention of respiratory syncytial virus

Loss of T-bet confers survival advantage to influenza-bacterial superinfection

Dual roles of IL-27 in cancer biology and immunotherapy

Specific increase in local IL-17 production during recovery from primary RSV bronchiolitis

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ Tcell responses and disease progression

HIV virology and pathogenetic mechanisms of infection: A brief overview

Differential pattern of soluble immune markers in asymptomatic dengue, West Nile and Zika virus infections

Distinct immune response in two MERS-CoV-infected patients: Can we go from bench to bedside?

Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection

Antiviral treatment of hepatitis C, BMJ (Online)

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Functional role of interleukin 1β (IL-1β) in IL-1β-converting enzymemediated apoptosis

Structure and signalling in the IL-17 receptor family

STAT3 inhibition prevents lung inflammation, remodeling, and accumulation of Th2 and Th17 cells in a murine asthma model

LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I randomized, doubleblind, placebo-controlled, proof-of-concept study

Assessment of the role of interleukin 17A and interleukin 17F in chronic hepatitis C virus infection in Egyptian patients

IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia

High prevalence of Foxp3 and IL17 in MMRproficient colorectal carcinomas

Fulminant myocarditis. Nature Clinical Practice Cardiovascular Medicine

Comment on "hepatitis C Virus-Specific Th17 cells are suppressed by virus-induced TGF-β

Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

Respiratory syncytial virus infection in the absence of STAT1 results in airway dysfunction, airway mucus, and augmented IL-17 levels

The impact of serum interleukin-17 on chronic hepatitis C and its sequelae

Seminal plasma HIV-1 RNA concentration is strongly associated with altered levels of seminal plasma interferon-γ, interleukin-17, and interleukin-5

Subversion of innate and adaptive immunity: Immune evasion from antibody and complement

Interleukin-6 (IL-6) and IL-17 synergistically promote viral persistence by inhibiting cellular apoptosis and cytotoxic T cell function

Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection

Respiratory syncytial virus exacerbates kidney damages in IgA nephropathy mice via the C5a-C5AR1 axis orchestrating Th17 cell responses

IL-17 Activates the IL-6/STAT3 Signal pathway in the proliferation of hepatitis B virus-related hepatocellular carcinoma

Articles clinical features of patients infected with 2019 novel coronavirus in Wuhan

IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis

Secukinumab: A new treatment option for psoriatic arthritis

Elevated macrophage inflammatory protein 1α and interleukin-17 production in an experimental asthma model infected with respiratory syncytial virus

IL-17 level in patients with dengue virus infection & its association with severity of illness

Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus

IL-17 stimulates the production and expression of proinflammatory cytokines, IL-β and TNF-α, by human macrophages

Genome of human hepatitis C virus (HCV): Gene organization, sequence diversity, and variation, Microbial and Comparative Genomics

Modulation of bronchial epithelial cells by IL-17

Association of polymorphisms in inflammatory cytokines encoding genes with severe cases of influenza A/H1N1 and B in an Iranian population

Transcription factor KLF10 constrains IL-17-committed Vγ4+ γδ T cells

Detection and analysis of disease-associated single nucleotide polymorphism influencing posttranslational modification

IL-22 exacerbates the severity of CVB3-induced acute viral myocarditis in IL-17A-deficient mice

Innate immune response to viral infection

Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice

Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses

Complications and outcomes of pandemic 2009 influenza A (H1N1) virus infection in hospitalized adults: How do they differ from those in seasonal influenza

Cytokine response patterns in severe pandemic 2009 h1n1 and seasonal influenza among hospitalized adults

IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A (H1N1) Virus

Significance of the balance between regulatory T (Treg) and T helper 17 (Th17) cells during hepatitis B virus related liver fibrosis

IL17A gene polymorphisms, serum IL-17A and IgE levels, and hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection

Early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia

Effects of Th17/Treg cell imbalance on HIV replicationin patients with AIDS

Human papillomavirus infection correlates with inflammatory stat3 signaling activity and IL-17 level in patients with colorectal cancer

Hepatitis B: The virus and disease

Erratum: Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3

The whole genome sequence of Coxsackievirus B3 MKP strain leading to myocarditis and its molecular phylogenetic analysis

Cellular immune response of dengue virus infection at different phases

Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis

The SNP rs4252548 (R112H) which is associated with reduced human height compromises the stability of IL-11

Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditis

Longitudinal study of cellular and systemic cytokine signatures to define the dynamics of a balanced immune environment during disease manifestation in zika virus-infected patients

Increased interleukin-17 production both in helper T cell subset Th17 and CD4-negative T cells in human immunodeficiency virus infection

IL-17 expression in human herpetic stromal keratitis: Modulatory effects on chemokine production by corneal fibroblasts

MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile

Cellular and cytokine correlates of severe dengue infection

The role of Th17 and Treg responses in the pathogenesis of RSV infection

A pharmacologically immunosuppressed mouse model for assessing influenza B virus pathogenicity and oseltamivir treatment

Interleukin-17 expression in the serum and exfoliated cervical cells of patients infected with high-risk oncogenic human papillomavirus

A human huntingtin SNP alters posttranslational modification and pathogenic proteolysis of the protein causing Huntington disease

The IL-17 family of cytokines in health and disease

Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: A 24-week, randomised, double-blind, placebo-controlled, phase ii proof-of-concept trial

IL-17 plays a role in respiratory syncytial virus-induced lung inflammation and emphysema in elastase and LPS-injured Mice

Molecular evolution of herpes simplex virus 2 complete genomes: Comparison between primary and recurrent infections

Targeting IL-17 and T H 17 cells in chronic inflammation

Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer

IL-17 receptor signaling influences virus-induced corneal inflammation

Gene expression in human macrophages infected with dengue virus serotype-2

Plasma levels of ifn-γ, il-4, il-6 and il-17 in hiv-positive patients with oral candidiasis

IL-17 induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease

Human immunodeficiency virus infection impairs Th1 and Th17 mycobacterium tuberculosis-specific T-Cell responses

Zika virus

Suppression of HIV-1 plasma viral load below detection preserves IL-17 producing T cells in HIV-1 infection

IL-17A inhibits airway reactivity induced by respiratory syncytial virus infection during allergic airway inflammation

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): An update

Immunity and fibrogenesis: The role of Th17/IL-17 axis in HBV and HCV-induced chronic hepatitis and progression to cirrhosis

A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17

IL-6 Promotes NK Cell Production of IL-17 during Toxoplasmosis

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The authors are thankful to the Department of Microbiology, All India Institute of Medical Sciences Bhopal (Madhya Pradesh), India. This work is supported by DBT-Ramalingaswami Re-entry grant no.