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.
Highlights
Interleukin-22 (IL-22) is a cytokine of IL-10 family with significant proliferative effect on different cell lines
In MTT and Carboxy fluorescein succinimidyl ester (CFSE) dilution assays, recombinant IL-22 (rIL-22) (MTT, observed with rIL-22 (OD): 1.27 ± 0.06) induced significant proliferation of Fibroblast like synoviocytes (FLS) derived from psoriatic arthritis (PsA) patients compared to media (OD: 0.53 ± 0.02), p < 0.001
Anti IL-22R antibody significantly inhibited the proliferative effect of rIL-22
Summary
Interleukin-22 (IL-22) is a cytokine of IL-10 family with significant proliferative effect on different cell lines. We are reporting the functional role of IL-22 in the inflammatory and proliferative cascades of psoriatic arthritis (PsA). Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis [1,2]. In the joint of PsA patients, there is hyperplasia of synovial lining cells and infiltration of mononuclear cells, which plays an important role in disease pathogenesis [5]. In PsA activated T cells produce increased amount of pro-inflammatory cytokines like IL-1b, IL-2, IFN-g, TNF-a and IL17 in the synovial fluid (SF) and contribute significantly to the disease pathogenesis [6,7,8]. IL-22, a newly discovered Th17 cytokine belongs to cytokine of IL-10 family, differs from other cytokines of IL-10 family by being a potent proliferative and inflammatory agent for different cell lines [16,17,18,19,20]. In collagen induced arthritis animal model, IL-22 has been found to play an important role in pannus formation as well as in osteoclastogenesis [29]
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