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O018 CCR6+ T helper cells drive antigen-induced arthritis via the IL-23R pathway
  1. W Razawy1,
  2. PS Asmawidjaja1,
  3. A-M Mus1,
  4. N Salioska1,
  5. M Van Meurs2,
  6. I Haspels-Brouwers2,
  7. N Kops3,
  8. E Lubberts1,
  9. on behalf of Rheumatology
  1. 1Rheumatology
  2. 2Immunology
  3. 3Orthopedics, Erasmus Medical Centre, Rotterdam, Netherlands


Introduction The IL-23/IL-17A immune pathway is important for the progression of T cell-mediated arthritis. However, it is not known where IL-23R+ T cells locate at different stages of arthritis and which IL-23R+ cells are drivers of joint inflammation.

Objectives We aimed to identify IL-23R+ T cells in the secondary lymphoid organs and synovium during the development and progression of antigen-induced arthritis (AIA). Furthermore, we studied which IL-23R+ cells drive full-blown AIA.

Methods To induce AIA, IL-23R+/+ (wild type), heterozygous IL-23R+/GFP (IL-23R-GFP.KI reporter), and IL-23RGFP/GFP (IL-23RKO) mice were immunised with methylated bovine serum albumin (mBSA) in Complete Freund’s Adjuvant. After 7 days mice were injected in the knee joints with mBSA. Mice were macroscopically scored and knees were used for histological analysis of inflammation and bone erosion. The spleen, inguinal and popliteal lymph nodes, and the synovium were collected and assessed for expression of GFP/IL-23R+ cells. Adoptive transfer of CCR6+ T helper cells and γδ T cells from heterozygous mice into IL-23RKO mice was performed via i.v. injection prior to AIA induction.

Results AIA disease progression was mainly driven by the IL-23R pathway as IL-23RKO mice had significantly lower arthritis scores and less bone damage. Heterozygous mice had similar disease scores to WT mice, indicating that half of the receptor expression is sufficient to drive disease. Flow cytometric analysis of GFP/IL-23R expression revealed that among the T cells, CCR6+ T helper and γδ T cells but not CD8+ T cells expressed the IL-23R in the lymphoid tissues. During the progressive phase of arthritis, lymphoid tissue cell numbers were lower in IL-23RKO mice. On the other hand, the overall percentage of T cells was higher in the IL-23RKO lymphoid tissues, suggesting that these cells develop but remain in the lymphoid tissues. CD4+ and γδ T cells but not CD8+ T cells were abundantly present in the WT joints during arthritis, but decreased in IL-23RKO joints. Adoptive transfer of CCR6+ T helper and γδ T cells into IL-23RKO mice revealed that CCR6+ T helper cells are the main drivers of AIA.

Conclusions AIA progression is driven by IL-23R signalling and CCR6 +T helper cells can rescue arthritis in IL-23R deficient mice. Among the T cells, only CCR6+ T helper and γδ T cells express the IL-23R in the lymphoid tissues. IL23R signalling might be involved in T cell proliferation and/or migration, since CD4+ and γδ T cell infiltration is decreased in the IL-23RKO synovium.

Disclosure of interest None declared

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