Severe CD4 T Cell-Mediated Immunopathology in Murine Schistosomiasis Is Dependent on IL-12p40 and Correlates with High Levels of IL-17

Rutitzky, Laura I.; Rosa, Jessica R. Lopes da; Stadecker, Miguel J.

doi:10.4049/jimmunol.175.6.3920

Cited by 164 publications

(200 citation statements)

References 35 publications

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“…However, the involvement of IL-17A in granuloma formation is not restricted to bacterial infection. The infection of mice with Schistosoma mansoni postimmunization with S. mansoni egg Ag induces severe granulomas, and the immunopathology depended on IL-17A (48). In contrast to mycobacterial infection, the IL-17A-producing cells were S. mansoni Ag-specific T cells.…”

Section: Discussionmentioning

confidence: 97%

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

Yoshida

Umemura

Yahagi

et al. 2010

The Journal of Immunology

348

261

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Granulomas play an essential role in the sequestration and killing of mycobacteria in the lung; however, the mechanisms of their development and maturation are still not clearly understood. IL-17A is involved in mature granuloma formation in the mycobacteria-infected lung. Therefore, IL-17A gene-knockout (KO) mice fail to develop mature granulomas in the Mycobacterium bovis bacille Calmette-Guérin (BCG)-infected lung. This study analyzed the mechanism of IL-17A–dependent mature granuloma formation in the mycobacteria-infected lung. The IL-17A KO mice showed a normal level of nascent granuloma formation on day 14 but failed to develop mature granulomas on day 28 after the BCG infection in the lung. The observation implies that IL-17A is required for the maturation of granuloma from the nascent to mature stage. TCR γδ T cells expressing TCR Vγ4 or Vγ6 were identified as the major IL-17A–producing cells that resided in the BCG-induced lung granuloma. The adoptive transfer of the IL-17A–producing TCR γδ T cells reconstituted granuloma formation in the IL-17A KO mice. The expression of ICAM-1 and LFA-1, which are adhesion molecules important in granuloma formation, decreased in the lung of the BCG-infected IL-17A KO mice, and their expression was induced on BCG-infected macrophages in coculture with IL-17A–producing TCR γδ T cells. Furthermore, IL-17A KO mice showed not only an impaired mature granuloma formation, but also an impaired protective response to virulent Mycobacterium tuberculosis. Therefore, IL-17A produced by TCR γδ T cells plays a critical role in the prevention of M. tuberculosis infection through the induction of mature granuloma formation.

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Section: Discussionmentioning

confidence: 97%

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

Yoshida

Umemura

Yahagi

et al. 2010

The Journal of Immunology

348

261

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“…Mice infected with Schistosoma mansoni and then immunized with soluble schistosome egg antigens (SEA) in CFA develop severe egg-induced immunopathology, with granulomatous inflammation mediated by IL-17 [97]. Furthermore S. mansoni-infected IL-23p19 À/À mice with or mice treated with anti-IL-17 neutralizing antibody had significantly reduced hepatic granulomatous inflammation, suggesting that IL-17-producing T cells contribute to immunopathology [84].…”

Section: Role Of Il-17-secreting T Cells In Infectionmentioning

confidence: 99%

Induction, function and regulation of IL‐17‐producing T cells

2008

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Recent reports have provided convincing evidence that IL-17-producing T cells play a key role in the pathogenesis of organ-specific autoimmune diseases, a function previously attributed exclusively to IFN-c-secreting Th1 cells. Furthermore, it appears that IL-17-producing T cells can also function with Th1 cells to mediate protective immunity to pathogens. Although much of the focus has been on IL-17-secreting CD4 1 T cells, termed The main function of IL-17-secreting T cells is to mediate inflammation, by stimulating production of inflammatory cytokines, such as TNF-a, IL-1b and IL-6, and inflammatory chemokines that promote the recruitment of neutrophils and macrophages.Key words: Autoimmunity . IL-17 . Infection . Inflammation IntroductionMore than 20 years ago Mosmann and Coffman reported that distinct CD4 1 T-cell subtypes, termed Th1 and Th2 cells, could be distinguished on the basis of cytokine secretion and function [1]. The Th1-Th2 model provided a useful but simplistic basis for our understanding of the mechanisms of immunity to infection and also attempted to explain the role of T cells in the pathogenesis of autoimmunity and allergy/asthma. The original hypothesis was that IFN-g-secreting CD4 1 cells mediated protective immunity to intracellular pathogens by promoting macrophage activation and stimulating production of complement fixing and virus neutralizing antibodies, but also promoted inflammatory responses and mediated the pathology in certain autoimmune diseases. In contrast, CD4 1 T cells that secreted IL-4, IL-5, IL-10 and IL-13 were considered to be the main helper T cells providing help for B-cell production of antibody, especially IgG1 in mice, and mediated protective immunity to extracellular pathogens. These Th2 cells were also anti-inflammatory, controlling Th1 responses, but at the same time mediated allergic reactions and had an inflammatory and pathological role in asthma.The identification of additional T-cell subtypes has led to a shift in the Th1-Th2 paradigm and has helped to explain some anomalies in the original model. In the mid 1990s suppressor T cells were re-discovered as Treg cells and were shown to have a major role in controlling immune responses to self-antigens, thereby preventing autoimmunity. Furthermore, these cells rather than the reciprocal Th1 or Th2 populations were shown to be the major regulator of effector T cells, functioning to maintain self-tolerance, prevent autoimmunity and limit collateral damage during immune responses to pathogens [2,3].There were a number of other observations which could not be explained on the basis of the two Th1 and Th2 subtypes. Mini-ReviewDespite the assumption that Th1 cells mediated autoimmunity, mice deficient in IFN-g or IFN-g receptors were found to have increased susceptibility to EAE and collagen-induced arthritis (CIA) [4,5]. Furthermore, EAE was exacerbated in mice deficient in the Th1 polarizing cytokine, 7]. It was then discovered that mice deficient in the novel IL-12 family member, IL-23 were resistant to EAE [6]....

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“…IL-17A and IL-17F are important members of the IL-17 cytokine family preferentially produced by helper T 17 (Th17) cells, which are responsible for the pathogenic activity of the lineage of CD4+ effector cells and multiple proinflammatory mediators (Rutitzky et al, 2005;Ishigame et al, 2009 et al, 2010). However, subsequent replication studies for the association between IL-17A and IL-17F variants and gastric cancer risk are controversial (Shibata et al, 2009;Arisawa et al, 2012;Rafiei et al, 2013;Zhang et al, 2014;Zhu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of Associations between Interleukin-17 Gene Polymorphisms and Risk of Gastric Cancer

Sun

Liu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Previous studies have indicated that single nucleotide polymorphisms (SNPs) of the interleukin-17 (IL-17) gene are associated with an increased risk of gastric cancer. However, the findings were inconsistent. Materials and Methods: To provide a more reliable estimation of the association between SNPs in the IL-17 gene and the susceptibility to gastric cancer, we searched PubMed, CNKI, and Wan Fang databases and selected finally six studies covering 2,366 cases and 3,205 controls to perform a meta-analysis. Results: Statistical analyses showed that an rs2275913 polymorphism within the IL-17A gene was significantly associated with an increased risk of gastric cancer using a generalized odds ratio (ORG, a model-free approach). Moreover, we also found that the 'A' allele carriers of IL-17A rs2275913 had a significant link with clinicopathological features. However, no significant positive signals were observed in the association analysis of the rs3748067 and rs763780 polymorphisms with the risk of gastric cancer in IL-17A and IL-17F, respectively. Conclusions: Despite some limitations, the present meta-analysis provided a more precise estimation of the relationship between the IL-17 gene SNPs and gastric cancer risk compared with individual studies.

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Severe CD4 T Cell-Mediated Immunopathology in Murine Schistosomiasis Is Dependent on IL-12p40 and Correlates with High Levels of IL-17

Cited by 164 publications

References 35 publications

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

Induction, function and regulation of IL‐17‐producing T cells

Meta-analysis of Associations between Interleukin-17 Gene Polymorphisms and Risk of Gastric Cancer

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