IL-17 signaling in host defense and inflammatory diseases

Qian, Youcun; Kang, Zizhen; Liu, Caini; Li, Xiaoxia

doi:10.1038/cmi.2010.27

Cited by 88 publications

(65 citation statements)

References 71 publications

(76 reference statements)

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“…In a coculture assay of purified MAIT cells and mycobacterium-infected M⌽, MAIT cells were found to curtail growth of intracellular bacterial replication associated with the secretion of IFN-␥ and IL-17A, known mediators of immunity against intracellular and extracellular bacterial infection (17,19,22,42,47,63,80). Furthermore, the "first-line" production of IFN-␥ and IL-17A by innate lymphocytes is known to play an important role in bridging innate and adaptive immunity (3,21,36,46,51,67).…”

Section: Discussionmentioning

confidence: 99%

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

et al. 2012

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ABSTRACTMucosa-associated invariant T (MAIT) cells are a unique population of αβ T cells in mammals that reside preferentially in mucosal tissues and express an invariant Vα paired with limited Vβ T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression of the evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Usingin vitroassays, recent studies have shown that mouse and human MAIT cells are activated by antigen-presenting cells (APCs) infected with diverse microbes, including numerous bacterial strains and yeasts, but not viral pathogens. However, whether MAIT cells play an important, and perhaps unique, role in controlling microbial infection has remained unclear. To probe MAIT cell function, we show here that purified polyclonal MAIT cells potently inhibit intracellular bacterial growth ofMycobacterium bovisBCG in macrophages (MΦ) in coculture assays, and this inhibitory activity was dependent upon MAIT cell selection by MR1, secretion of gamma interferon (IFN-γ), and an innate interleukin 12 (IL-12) signal from infected MΦ. Surprisingly, however, the cognate recognition of MR1 by MAIT cells on the infected MΦ was found to play only a minor role in MAIT cell effector function. We also report that MAIT cell-deficient mice had higher bacterial loads at early times after infection compared to wild-type (WT) mice, demonstrating that MAIT cells play a unique role among innate lymphocytes in protective immunity against bacterial infection.

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Section: Discussionmentioning

confidence: 99%

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

et al. 2012

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“…Following the discovery of IL-17 and its biological functions, many studies have demonstrated that increased IL-17 expression is associated with inflammatory autoimmune diseases in either human patients or animal disease models [137,174,175]. Robust evidence shows that IL-17 mediates adverse effects in many autoimmune diseases such as RA, MS, SLE, IBD (inflammatory bowel disease) and psoriasis to name a few [176].…”

Section: Pathological Roles Of Il-17 In Autoimmune Diseasesmentioning

confidence: 97%

IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential

2012

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IL-17 (interleukin-17), a hallmark cytokine of Th17 (T-helper 17) cells, plays critical roles in host defence against bacterial and fungal infections, as well as in the pathogenesis of autoimmune diseases. The present review focuses on current knowledge of the regulation, functional mechanisms and targeting strategies of IL-17 in the context of inflammatory autoimmune diseases. Evidence shows that IL-17 is highly up-regulated at sites of inflammatory tissues of autoimmune diseases and amplifies the inflammation through synergy with other cytokines, such as TNF (tumour necrosis factor) α. Although IL-17 was originally thought to be produced mainly by Th17 cells, a newly defined T-cell subset with a specific differentiation programme and tight regulation, several other cell types (especially innate immune cells) are also found as important sources for IL-17 production. Although IL-17 activates common downstream signalling, including NF-κB (nuclear factor κB), MAPKs (mitogen-activated protein kinases), C/EBPs (CCAAT/enhancer-binding proteins) and mRNA stability, the immediate receptor signalling has been shown to be quite unique and tightly regulated. Mouse genetic studies have demonstrated a critical role for IL-17 in the pathogenesis of variety of inflammatory autoimmune diseases, such as RA (rheumatoid arthritis) and MS (multiple sclerosis). Importantly, promising results have been shown in initial clinical trials of monoclonal antibodies against IL-17 or its receptor (IL-17R) to block IL-17-mediated function in treating autoimmune patients with psoriasis, RA and MS. Therefore targeting IL-17/IL-17R, IL-17-producing pathways or IL-17-mediated signalling pathways can be considered for future therapy in autoimmune diseases.

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“…More IL-17-producing sources have now been found, especially innate immune cells (6,23). IL-17 belongs to a cytokine family containing six members (IL-17A to IL-17F) which are structurally different from other cytokines (7,8,16,26,40). IL-17 is the best-characterized member of the family.…”

mentioning

confidence: 99%

“…IL-17 is the best-characterized member of the family. IL-17 is a proinflammatory cytokine and acts on local tissue cells to induce production of genes for proinflammatory proteins, including cytokines, chemokines, and matrix metalloproteases, to amplify inflammation (8,16,26). The IL-17 level is elevated in a variety of inflammatory and autoimmune disorders, while IL-17 deficiency or its functional blockage reduces the development and pathogenesis of autoimmune diseases, suggesting that IL-17 is a promising target for various inflammatory disorders (16,26).…”

mentioning

confidence: 99%

TRAF6-Dependent Act1 Phosphorylation by the IκB Kinase-Related Kinases Suppresses Interleukin-17-Induced NF-κB Activation

Gao

Zhu

et al. 2012

Molecular and Cellular Biology

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IL-17 signaling in host defense and inflammatory diseases

Cited by 88 publications

References 71 publications

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential

TRAF6-Dependent Act1 Phosphorylation by the IκB Kinase-Related Kinases Suppresses Interleukin-17-Induced NF-κB Activation

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