Enrichment of circulating interleukin‐17–secreting interleukin‐23 receptor–positive γ/δ T cells in patients with active ankylosing spondylitis

Kenna, Tony J.; Davidson, Sean; Duan, Ran; Bradbury, L.; McFarlane, Janelle; Smith, Malcolm D.; Weedon, Helen; Street, Shayna E.A.; Thomas, Ranjeny; Thomas, Gethin; Brown, Matthew A.

doi:10.1002/art.33507

Cited by 239 publications

(183 citation statements)

References 58 publications

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“…gdT-17 cells enhance autoimmunity in the mouse model of multiple sclerosis (9,40), and an enrichment of these cells was observed in active disease in patients with ankylosing spondylitis (41). Furthermore, gd T cells are the predominant dermal cell producing IL-17 in murine psoriasis and are greatly increased in the skin lesions of psoriasis patients (42).…”

Section: Discussionmentioning

confidence: 99%

Differential Responsiveness of Innate-like IL-17– and IFN-γ–Producing γδ T Cells to Homeostatic Cytokines

Corpuz

Stolp

Kim

et al. 2016

The Journal of Immunology

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γδ T cells respond to molecules upregulated following infection or cellular stress using both TCR and non-TCR molecules. The importance of innate signals versus TCR ligation varies greatly. Both innate-like IL-17–producing γδ T (γδT-17) and IFN-γ–producing γδ T (γδT-IFNγ) subsets tune the sensitivity of their TCR following thymic development, allowing robust responses to inflammatory cytokines in the periphery. The remaining conventional γδ T cells retain high TCR responsiveness. We determined homeostatic mechanisms that govern these various subsets in the peripheral lymphoid tissues. We found that, although innate-like γδT-17 and γδT-IFNγ cells share elements of thymic development, they diverge when it comes to homeostasis. Both exhibit acute sensitivity to cytokines compared with conventional γδ T cells, but they do not monopolize the same cytokine. γδT-17 cells rely exclusively on IL-7 for turnover and survival, aligning them with NKT17 cells; IL-7 ligation triggers proliferation, as well as promotes survival, upregulating Bcl-2 and Bcl-xL. γδT-IFNγ cells instead depend heavily on IL-15. They display traits analogous to memory CD8+ T cells and upregulate Bcl-xL and Mcl-1 upon cytokine stimulation. The conventional γδ T cells display low sensitivity to cytokine-alone stimulation and favor IL-7 for their turnover, characteristics reminiscent of naive αβ T cells, suggesting that they may also require tonic TCR signaling for population maintenance. These survival constraints suggest that γδ T cell subsets do not directly compete with each other for cytokines, but instead fall into resource niches with other functionally similar lymphocytes.

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Section: Discussionmentioning

confidence: 99%

Differential Responsiveness of Innate-like IL-17– and IFN-γ–Producing γδ T Cells to Homeostatic Cytokines

Corpuz

Stolp

Kim

et al. 2016

The Journal of Immunology

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“…gdT17 cells have most recently been shown to participate in the immunopathology of a variety of inflammatory diseases in epithelial barrier tissues, including inflammatory bowel disease, psoriasis, and asthma (11,14,15), but also in spondylarthropathies and CNS inflammation in mouse models (1,16) and in humans (17)(18)(19). Because the presence of gdT17 cells in certain tissues might set the threshold for these tissues to respond directly to pathogen-associated molecular patterns and indirectly to the proinflammatory cytokine IL-23, the regulation of gdT17 cell populations during homeostasis and in inflammation is highly relevant in the context of immune interventions in autoimmune diseases, chronic inflammation, and inflammation associated with malignant disease.…”

mentioning

confidence: 99%

IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122− γδ T Cells to γδT17 Cells

Muschaweckh

Petermann

Korn

2017

The Journal of Immunology

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γδT17 cells are a subset of γδ T cells committed to IL-17 production and are characterized by the expression of IL-23R and CCR6 and lack of CD27 expression. γδT17 cells are believed to arise within a narrow time window during prenatal thymic development. In agreement with this concept, we show in this study that adult Rag1−/− recipient mice of Il23rgfp/+ (IL-23R reporter) bone marrow selectively lack IL-23R+ γδT17 cells. Despite their absence in secondary lymphoid tissues during homeostasis, γδT17 cells emerge in bone marrow chimeric mice upon induction of skin inflammation by topical treatment with imiquimod cream (Aldara). We demonstrate that IL-1β and IL-23 together are able to promote the development of bona fide γδT17 cells from peripheral CD122−IL-23R− γδ T cells, whereas CD122+ γδ T cells fail to convert into γδT17 cells and remain stable IFN-γ producers (γδT1 cells). IL-23 is instrumental in expanding extrathymically generated γδT17 cells. In particular, TCR-Vγ4+ chain–expressing CD122−IL-23R− γδ T cells are induced to express IL-23R and IL-17 outside the thymus during skin inflammation. In contrast, TCR-Vγ1+ γδ T cells largely resist this process because prior TCR engagement in the thymus has initiated their commitment to the γδT1 lineage. In summary, our data reveal that the peripheral pool of γδ T cells retains a considerable degree of plasticity because it harbors “naive” precursors, which can be induced to produce IL-17 and replenish peripheral niches that are usually occupied by thymus-derived γδT17 cells.

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“…W jelicie chorych na ZZSK nie ma jednak ekspansji komórek Th17, co może być spowodowane brakiem innych cytokin (IL-6, IL-1β) ukierunkowujących różnicowanie tych komórek, a IL-17 jest wytwarzana przez komórki odporności wrodzonej (neutrofile, limfocyty Tγ/δ). Liczba limfocytów Tγ/δ jest zwiększona także we krwi obwodowej chorych na ZZSK [43].…”

Section: Zaburzenia Homeostazy W Spondyloartropatiach Zapalnychunclassified

New aspects of spondyloarthritis pathogenesis. Part II – environmental factors, microbiome disturbances, extra-articular symptoms

Kontny¹

2014

Reumatologia

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Spondyloartropatie zapalne (SpA) to grupa chorób o podobnych cechach klinicznych i uwarunkowaniach genetycznych. Zakażenia bakteryjne układu pokarmowego i moczowo-płciowego są głównym czynnikiem środowiskowym związanym z rozwojem SpA. Nowe dane wskazują, że bakterie wewnątrzkomórkowe mogą rozprzestrzeniać zakażenie do innych miejsc anatomicznych. U chorych na SpA często występują objawy pozastawowe, zwłaszcza zapalenie jelit. Postęp w zrozumieniu roli mikrobioty jelitowej w homeostazie oraz nowe dane wskazujące na udział zaburzeń mikrobiomu w rozwoju różnych chorób pozwalają lepiej zrozumieć patogenezę SpA. Przypuszcza się, że SpA może się rozwijać na skutek przeniesienia do stawów odpowiedzi immunologicznej, która jest pierwotnie indukowana w jelicie. Przyczyną zapalenia jelit w SpA może być dysbioza, spowodowana przez czynniki genetyczne i środowiskowe.

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Enrichment of circulating interleukin‐17–secreting interleukin‐23 receptor–positive γ/δ T cells in patients with active ankylosing spondylitis

Cited by 239 publications

References 58 publications

Differential Responsiveness of Innate-like IL-17– and IFN-γ–Producing γδ T Cells to Homeostatic Cytokines

Differential Responsiveness of Innate-like IL-17– and IFN-γ–Producing γδ T Cells to Homeostatic Cytokines

IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122− γδ T Cells to γδT17 Cells

New aspects of spondyloarthritis pathogenesis. Part II – environmental factors, microbiome disturbances, extra-articular symptoms

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