Interleukin‐17 in rheumatoid arthritis: If T cells were to contribute to inflammation and destruction through synergy

Miossec, Pierre

doi:10.1002/art.10816

Cited by 248 publications

(174 citation statements)

References 53 publications

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“…infection with E. coli. IL-17 has also been shown to be involved in autoimmune disease, such as rheumatoid arthritis (22). It is of note that the majority of the infiltrating cells in the synovial fluid of rheumatoid arthritis are neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Resident Vδ1+ γδ T Cells Control Early Infiltration of Neutrophils after Escherichia coli Infection via IL-17 Production

Shibata

Yamada

Hara

et al. 2007

The Journal of Immunology

441

410

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Neutrophils infiltrate the site of infection and play critical roles in host defense, especially against extracellular bacteria. In the present study, we found a rapid and transient production of IL-17 after i.p. infection with Escherichia coli, preceding the influx of neutrophils. Neutralization of IL-17 resulted in a reduced infiltration of neutrophils and an impaired bacterial clearance. Ex vivo intracellular cytokine flow cytometric analysis revealed that γδ T cell population was the major source of IL-17. Mice depleted of γδ T cells by mAb treatment or mice genetically lacking Vδ1 showed diminished IL-17 production and reduced neutrophil infiltration after E. coli infection, indicating an importance of Vδ1+ γδ T cells as the source of IL-17. It was further revealed that γδ T cells in the peritoneal cavity of naive mice produced IL-17 in response to IL-23, which was induced rapidly after E. coli infection in a TLR4 signaling-dependent manner. Thus, although γδ T cells are generally regarded as a part of early induced immune responses, which bridge innate and adaptive immune responses, our study demonstrated a novel role of γδ T cells as a first line of host defense controlling neutrophil-mediated innate immune responses.

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Section: Discussionmentioning

confidence: 99%

Resident Vδ1+ γδ T Cells Control Early Infiltration of Neutrophils after Escherichia coli Infection via IL-17 Production

Shibata

Yamada

Hara

et al. 2007

The Journal of Immunology

441

410

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“…Studies in IL-17 receptor knockout mice revealed a critical role of IL-17 receptor signaling in driving synovial expression of proinflammatory and catabolic mediators, such as IL-1 and different MMPs leading to less cartilage damage and bone erosion in experimental arthritis [11,31]. Similar as for joint inflammation, additive/synergistic catabolic effects were noted between IL-17 and IL-1/TNF [29,32,33]. In vitro, IL-17 suppresses matrix synthesis by articular chondrocytes through enhancement of nitric oxide (NO) production [26,[34][35][36].…”

Section: Experimental Arthritis Studiesmentioning

confidence: 99%

IL-17/Th17 targeting: On the road to prevent chronic destructive arthritis?

Lubberts¹

2008

Cytokine

274

230

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Interleukin-17A (IL-17A) contributes to the pathogenesis of arthritis. Data from experimental arthritis indicate IL-17 receptor signaling as a critical pathway in turning an acute synovitis into a chronic destructive arthritis. The identification of six IL-17 family members (IL-17A-F) may extend the role of this novel cytokine family in the pathogenesis of chronic destructive joint inflammation. Whether the successful anti-IL-17A cytokine therapy in murine arthritis can be effectively translated to human arthritis need to be tested in clinical trials in humans. Interestingly, IL-17A and IL-17F are secreted by the novel T helper subset named Th17. This novel pathogenic T cell population induces autoimmune inflammation in mice and is far more efficient at inducing Th1-mediated autoimmune inflammation in mice than classical Th1 cells (IFN-c). In addition to IL-17A and IL-17F, Th17 cells are characterized by expression of IL-6, TNF, GM-CSF, IL-21, IL-22 and IL-26. Th17 cells have been established as a separate lineage of T helper cells in mice distinct from conventional Th1 and Th2 cells. Whether this also applies to human Th17 and whether RA is a Th1 or a Th17 mediated disease is still not clear. This review summarizes the findings about the role of IL-17 in arthritis and discusses the impact of the discovery of the novel Th17 cells for arthritis. Further studies are needed to unravel the role of Th17 cells and the interplay of IL-17 and other Th17 cytokines in the pathogenesis of arthritis and whether regulating Th17 cell activity will have additional value compared to neutralizing IL-17A activity alone. This might help to reach the ultimate goal not only to treat RA patients but to prevent the development of this crippling disease.

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“…I L-17 (IL-17A) is a proinflammatory cytokine critical for the development of various autoimmune diseases (1)(2)(3)(4). IL-17 also plays a role in host defense against various pathogens especially by inducing mobilization of neutrophils (5).…”

mentioning

confidence: 99%

Identification of CD25+ γδ T Cells As Fetal Thymus-Derived Naturally Occurring IL-17 Producers

Shibata

Yamada

Nakamura

et al. 2008

The Journal of Immunology

164

189

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We previously reported that resident γδ T cells in the peritoneal cavity rapidly produced IL-17 in response to Escherichia coli infection to mobilize neutrophils. We found in this study that the IL-17-producing γδ T cells did not produce IFN-γ or IL-4, similar to Th17 cells. IL-17-producing γδ T cells specifically express CD25 but not CD122, whereas CD122+ γδ T cells produced IFN-γ. IL-17-producing γδ T cells were decreased but still present in IL-2- or CD25-deficient mice, suggesting a role of IL-2 for their maintenance. IFN-γ-producing CD122+ γδ T cells were selectively decreased in IL-15-deficient mice. Surprisingly, IL-17-producing γδ T cells were already detected in the thymus, although CD25 was not expressed on the intrathymic IL-17-producing γδ T cells. The number of thymic IL-17-producing γδ T cells was peaked at perinatal period and decreased thereafter, coincided with the developmental kinetics of Vγ6+Vδ1+ γδ T cells. The number of IL-17-producing γδ T cells was decreased in fetal thymus of Vδ1-deficient mice, whereas Vγ5+ fetal thymocytes in normal mice did not produce IL-17. Thus, it was revealed that the fetal thymus-derived Vγ6+Vδ1+ T cells functionally differentiate to produce IL-17 within thymus and thereafter express CD25 to be maintained in the periphery.

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Interleukin‐17 in rheumatoid arthritis: If T cells were to contribute to inflammation and destruction through synergy

Cited by 248 publications

References 53 publications

Resident Vδ1+ γδ T Cells Control Early Infiltration of Neutrophils after Escherichia coli Infection via IL-17 Production

Resident Vδ1+ γδ T Cells Control Early Infiltration of Neutrophils after Escherichia coli Infection via IL-17 Production

IL-17/Th17 targeting: On the road to prevent chronic destructive arthritis?

Identification of CD25+ γδ T Cells As Fetal Thymus-Derived Naturally Occurring IL-17 Producers

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