Background/Purpose:

IL-22,belongs to the IL-10 family of cytokines and is primarily produced by CD4 T, NK and LTi cells. IL-22 plays a dual role depending on the context of the disease model under study, it is protective in inflammatory bowel disease, hepatitis, myocarditis, ulcerative colitis and pathogenic in psoriasis. IL-22 knock-out mice have a reduced incidence of arthritis, while neutralization of IL-22 after onset of arthritis in IL-1 receptor antagonist knock-out mice had limited effect on joint inflammation, additionally, administration of IL-22 prior to onset of joint inflammation is associated with reduced arthritis. These findings are suggestive of a nuanced role of IL-22 in the regulation of inflammation.

Methods: CIA was induced in DBA1 mice following immunization with collagen and complete Freund’s adjuvant. Arthritic mice with clinical scores of   ≥ 1 and with arthritis duration of 4 days were randomized to receive anti-IL-22 or RatIgG antibody and disease progression was assessed by clinical scoring and histopathology. IL-22, IL-17 and IFN-g responses were measured by ELISA and flowcytometry. Anti-collagen antibodies were analyzed by ELISA. Expression of IL-22R1 in CD4T, CD19+ and CD11c+ cells was elucidated by flowcytometry and real time PCR

Results:

There was a significant expansion of collagen specific IL-22 responses during arthritis and IL-22 producing cells were discrete from IL-17 or IFN-g producing cells. Neutralization of IL-22 after onset of joint inflammation resulted in significantly reduced severity of arthritis and was accompanied by increase in collagen specific IFN-g responses, a modest reduction of anti-collagen IgG2a antibodies, and unaltered Th17 or IL-10 responses. To corroborate our findings, both intracellular and secreted levels of IFN-γ and IL-17 were measured and similar results were observed. CD4+T cells from arthritic mice showed increase surface expression of IL-22R1(13.3%) in comparison to naïve mice (1.50%) or mice from the initiation phase (1.97%). Flowcytometrically, IL-22R1 was detectable in CD19+ cells, however, the expression levels were similar in naïve mice, mice from initiation phase or arthritic mice .In-vitro, CD4T cells from arthritic mice when co-cultured with antigen presenting cells in the presence or absence of IL-22, suppressed or induced IFN-g respectively. In another in-vitro set up, CD19 cells from arthritic mice when cultured in the presence of recombinant IL-22, showed significant suppression of anti-collagen IgG1 and augmentation of IgG2a responses. These in vitro results are in agreement with our in vivo findings suggesting that IL-22R1 expression in T and B cells is functionally active and associated with IFN-g regulation in T cells or pathogenic anti-collagen IgG2a antibody production from B cells.  Our results shows that IL-22R1 may be induced on immunocytes during inflammatory state thus enabling them to respond to IL-22.

Conclusion:

Endogenous IL-22 suppresses Th1 responses and is pathogenic after onset of arthritis. IL-22R1 is upregulated in CD4 T cells during arthritis and regulates IFN-g in T cells.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/endogenous-il-22-regulates-th1-responses-and-plays-a-pathogenic-role-after-the-onset-of-arthritis/