Background/Purpose: IL-22 is an IL-10 family cytokine with both pro-inflammatory and anti-inflammatory effects and its dysregulation is associated with the development of autoimmune disease including psoriasis, rheumatoid arthritis and Crohn’s disease. The purpose of this study was to characterize the role of IL-22 production from CD4 T cells in psoriatic arthritis (PsA).

Methods: Whole PBMCs from PsA patients and healthy controls (HCs) were stimulated with anti-CD3/CD28 (αCD3/28) and cultured for 3 or 5 days. CD4+ T cell populations were analysed for surface expression of CCR6, CXCR3, CCR4 and CCR10 and intracellular production of IL-22, IFN-γ and IL-17 measured by FACS. The percentage of IL-22+IL-17- cells within CD4+ T cells after 5 days culture were correlated with percentage naïve (CD27CD45RA+), central memory (CD27⁺ CD45RA^–), and effector memory (CD27- CD45RA-). CD4 T cell subsets were isolated, and IL-22 and IFN-γ production from HCs and PsA patients measured by FACS and the concentration in the T cell supernatants quantified by ELISA. The effects of IL-22 and IFN-γ were investigated using the HaCaT keratinocyte cell line as a model of inflammation.

Results: In the peripheral blood of untreated PsA patients, there was an overall decrease in the percentage IL-22⁺CD4⁺ T-cells compared to HCs (p=0.0075). This was associated with a switch from an IL-22-producing central memory cells in HCs, towards effector memory cells capable of accumulating at sites of inflammation in PsA. Paradoxically, we found a significant increase in IL-22 (p=0.026) and IFN-γ (p=0.001) production by naïve T cells from patients with PsA upon stimulation associated with increased proliferation (p=0.01) compared to healthy controls. This aberrant control of IL-22 and IFN-γ in the naïve T cell subset was restored in adalimumab treated patients. IL-22⁺CD4+ T-cells in HCs expressed CCR6 whereas there was a significant loss of CCR6 expression in CD4 T cells in untreated PsA patients (p=0.0027) but not adalimumab treated patients. Supernatants from anti-CD3/28+/-IL-21 stimulated naïve T cells from untreated PsA patients, but not patients treated with adalimumab, induced high levels of the T cell chemoattractant CXCL-9 in HaCaT cells compared to HCs (p=0.0079) in an IFN-γ dependent manner. Moreover, blockade of IL-22 in supernatants from anti-CD3/28 +IL-21 activated naïve T cells from untreated PsA patients enhanced the production of CXCL-9 from HaCaT cells (p=0.01), suggesting an ability of IL-22 to negatively regulate IFN-γ.

Conclusion: IL-22 and IFN-γ production is dysregulated in PsA. IL-22+ CD4+ T cells switch to an effector memory phenotype and show an altered migratory phenotype which may promote accumulation of these cells at sites of inflammation. Furthermore IL-22 can act to suppress pathogenic responses triggered by IFN-γ suggesting that IL-22 may play a protective role in PsA. Modulation of this axis may therefore be a potential target for therapy in in PsA.

« Back to ACR/ARHP Annual Meeting 2016

ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-22-is-dysregulated-in-psoriatic-arthritis-and-acts-to-limit-ifn-%ce%b3-driven-inflammatory-chemokine-production/