Functional role of IL-22 in psoriatic arthritis

Abstract

IntroductionInterleukin-22 (IL-22) is a cytokine of IL-10 family with significant proliferative effect on different cell lines. Immunopathological role of IL-22 has been studied in rheumatoid arthritis (RA) and psoriasis. Here we are reporting the functional role of IL-22 in the inflammatory and proliferative cascades of psoriatic arthritis (PsA).MethodFrom peripheral blood and synovial fluid (SF) of PsA (n = 15), RA (n = 15) and osteoarthritis (OA, n = 15) patients, mononuclear cells were obtained and magnetically sorted for CD3+ T cells. Fibroblast like synoviocytes (FLS) were isolated from the synovial tissue of PsA (n = 5), RA (n = 5) and OA (n = 5) patients. IL-22 levels in SF and serum were measured by enzyme linked immunosorbent assay (ELISA). Proliferative effect of human recombinant IL-22 (rIL-22) on FLS was assessed by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole) and CFSE dilution (Carboxyfluorescein succinimidyl ester) assays. Expression of IL-22Rα1 in FLS was determined by western blot.ResultsIL-22 levels were significantly elevated in SF of PsA patients (17.75 ± 3.46 pg/ml) compared to SF of OA (5.03 ± 0.39 pg/ml), p < 0.001. In MTT and CFSE dilution assays, rIL-22 (MTT, OD: 1.27 ± 0.06) induced significant proliferation of FLS derived from PsA patients compared to media (OD: 0.53 ± 0.02), p < 0.001. In addition, rIL-22 induced significantly more proliferation of FLS in presence of TNF-α. IL-22Rα1 was expressed in FLS of PsA, RA and OA patients. Anti IL-22R antibody significantly inhibited the proliferative effect of rIL-22. Further we demonstrated that activated synovial T cells of PsA and RA patients produced significantly more IL-22 than those of OA patients.ConclusionSF of PsA patients have higher concentration of IL-22 and rIL-22 induced marked proliferation of PsA derived FLS. Moreover combination of rIL-22 and TNF-α showed significantly more proliferative effect on FLS. IL-22Rα1 was expressed in FLS. Successful inhibition of IL-22 induced FLS proliferation by anti IL-22R antibody suggests that blocking of IL-22/IL-22R interaction may be considered as a novel therapeutic target for PsA.

Cytokines in Graft-versus-Host Disease

“…Novel targets, such as IL-32, IL-34, and IL-35, are also being explored (92). The success of cytokine inhibition in rheumatoid arthritis is also paralleled in other inflammatory diseases, including psoriatic dermatitis and arthritis (93), with TNF inhibition having a demonstrated role, in addition to promising newer targets, such as IL-22 and IL-23 (94,95). Evidence for the value of cytokine inhibition exists in diseases other than inflammatory arthropathies, with efficacy demonstrated for TNF (96), as well as IL-12/23 (97,98), in inflammatory bowel disease.…”

Interleukin 22, a Potential Therapeutic Target for Rheumatoid Arthritis

“…The IL-22 concentration in synovial fluid was higher in patients with RA compared with controls 2,3 . In patients with RA, Th17 cells were recognized to produce higher IL-22 4 .…”

“…In addition, natural killer (NK)-22 cells in vitro can secrete higher levels of IL-22 and tumor necrosis factor-α (TNF-α), and NK-22 supernatant can induce the proliferation of RA fibroblast-like synoviocytes (FLS); however, addition of IL-22 antibody plus TNF-α antibody inhibited the proliferation of FLS induced by the NK-22 supernatant 7 . In vitro, human recombinant IL-22 (rhIL-22) significantly increased proliferation of RA synovial fluid and FLS and production of monocyte chemoattractant protein-1 3,7,8 , but an inhibitory effect of anti-IL-22R antibody on proliferation of FLS induced by rhIL-22 was found in RA 3 . Moreover, an experimental arthritis model (IL-1Ra−/−) displayed a progressive erosive arthritis characterized by upregulation of IL-22 in severely inflamed synovia; and anti-IL-22 treatment of IL-1Ra−/− mice significantly reduced the inflammation and bone erosions 9 .…”

L.F. da Rocha Jr, et al reply

“…The association of IL-22 with bone erosions supports the idea that this cytokine may play a role in destructive bone disease. IL-22 may also be associated with pannus formation 4 .…”

“…Knowledge about the role of IL-22 in autoimmune diseases is increasing and may reveal new therapeutic options for modulation of this cytokine. The role of IL-22 has been investigated in other inflammatory autoimmune diseases, such as psoriasis 3 and psoriatic arthritis 4 , systemic sclerosis 5 , and systemic lupus erythematosus 6 .…”