Th17 and Th22 cells in psoriatic arthritis and psoriasis

Abstract

IntroductionThe aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA).MethodsFlow cytometry was used to enumerate cells making IL-22 and IL-17, in skin and/or SF and PB from 11 patients with Ps and 12 patients with PsA; skin and PB of 15 healthy controls and SF from rheumatoid arthritis (RA) patients were used as controls. Expression of the interleukin 23 receptor (IL-23R) and chemokine receptors CCR4 and CCR6 was examined. Secretion of IL-17 and IL-22 was measured by ELISA. ST was analysed by immunohistochemical staining of IL-17 and IL-22.ResultsIncreased frequencies of IL-17+ and IL-22+ CD4+ T cells were seen in PB of patients with PsA and Ps. IL-17 secretion was significantly elevated in both PsA and Ps, whilst IL-22 secretion was higher in PsA compared to Ps and healthy controls. A higher proportion of the CD4+ cells making IL-17 or IL-22 expressed IL-23R and frequencies of IL-17+, CCR6+ and CCR4+ T cells were elevated in patients with Ps and those with PsA. In patients with PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB. Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were demonstrated in Ps skin lesions. In contrast, whilst elevated frequencies of CD4+ IL-17+ cells were seen in PsA SF compared to PB, frequencies of CD4+ IL-22+ T cells were lower. Whereas IL-17 expression was equivalent in PsA, osteoarthritis (OA) and RA ST, IL-22 expression was higher in RA than either OA or PsA ST, in which IL-22 was strikingly absent.ConclusionsElevated frequencies of IL-17 and IL-22 producing CD4+ T cells were a feature of both Ps and PsA. However their differing distribution at disease sites, including lower frequencies of IL-22+ CD4+ T cells in SF compared to skin and PB, and lack of IL-22 expression in ST suggests that Th17 and Th22 cells have common, as well as divergent roles in the pathogenesis of Ps and PsA.

Positive-Negative Feedback Loop between Mir-197 and IL-17A Signaling in Human Keratinocytes

“…An increased number of Th17 cells have been identified in the dermis and epidermis of psoriatic skin compared with normal skin, which supports the central role that IL-17A plays in the pathogenesis of psoriasis [7][8][9]. Results from recent clinical trials have confirmed the central contribution of IL-17A to psoriasis.…”

Cytokines as Therapeutic Targets in Rheumatoid Arthritis and Other Inflammatory Diseases

“…Animal models clearly support the IL-17/IL-23 axis in both the skin and joint aspects of disease pathology in PsA. Furthermore, the evaluation of clinical samples has demonstrated that elevated IL-17 and IL-23 is present in the psoriatic skin and synovial fluid of PsA patients (Benham et al, 2013).…”

Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

“…12 Th17 cells promote autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disorders and psoriasis as well. 13 Moreover, as reported above, Th17 and, more recently, Th22 cells have been studied in the context of several tumors. 5,14 …”