CD4 T-Cell Dysregulation in Psoriatic Arthritis Reveals a Regulatory Role for IL-22.

ABSTRACT: Dysregulation of interleukin-22 (IL-22) has been associated with autoimmune diseases but divergent effects upon inflammation have hampered efforts to define its contribution to pathogenesis. Here, we examined the role of IL-22 in patients with psoriatic arthritis (PsA). In the peripheral blood of PsA patients, there was a decrease in IL-22⁺CD4⁺ T cells compared with healthy controls resulting in a heightened CD4⁺ IFN?⁺/IL-22⁺ ratio accompanied by diminished CCR6 expression. IL-22 expressing cells were depleted primarily from the central memory CD4 T-cell subset in PsA patients. Paradoxically IL-22 and particularly interferon-gamma (IFN?) production were elevated within a CD4⁺ T-cell subset with phenotypic markers characteristic of naïve T cells (CD3⁺CD4⁺CD27⁺CD45RA⁺CCR7⁺CD95^-IL-2R?^-) from PsA patients with the highest IFN?⁺/IL-22⁺ ratio of all the CD4 subsets. These unconventional "naïve" CD4⁺ T cells from PsA patients displayed some phenotypic and functional characteristics of memory cells including a marked proliferative response. Increased IFN? production from these unconventional "naïve" T cells from PsA patients promoted greater expression of the chemo-attractant CXCL9 by HaCaT keratinocytes compared with their healthy counterparts. Treatment with anti-TNF therapy reversed these abnormalities in this T-cell subset though did not affect the frequency of IL-22⁺ T cells overall. Furthermore, blockade of IL-22 enhanced the IFN? mediated release of CXCL-9. These results reveal CD4⁺ T-cell dysregulation in patients with PsA which can be reversed by anti-TNF and highlight the regulatory properties of IL-22 with important implications for therapeutic approaches that inhibit its production.

SUBMITTER: Ezeonyeji A 

PROVIDER: S-EPMC5666299 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature