Exploring the role of interleukin-22 in neurological and autoimmune disorders. International immunopharmacology Interleukin-22 (IL-22) is a member of the IL-10 cytokine family that has recently gained attention in regard to its recognized pathogenic role in neurological and autoimmune disorders. The pathological involvement of IL-22 has been linked to Th17 cells that are involved in its production. Its biological activity results from its ability to bind to a heterodimeric receptor consisting of IL-22 receptor 1 (IL-22R1) and IL-10R2. Emerging evidence has identified IL-22 involvement in neurological diseases and autoimmune disorders such as Guillain-Barré Syndrome (GBS), multiple sclerosis (MS), Alzheimer's disease (AD), encephalitis, inflammatory myopathies, myasthenia gravis (MG), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), psoriasis and Crohn's disease (CD). However, the biological activity of IL-22 is variable resulting in protective or pathogenic effects in different disease states. As such, the development of therapeutic targeting strategies to modify the biological activity of IL-22 is being explored as a promising interventional approach to treat neurological and autoimmune diseases. 10.1016/j.intimp.2015.08.016

IL-22 production of effector CD4 T-cells is altered in SLE patients. European journal of medical research BACKGROUND:Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T-cell-dependent B-cell activation and altered T-cell response. Co-stimulatory and co-inhibitory molecules regulate and exert T-cell differentiation, survival and cytokine production. CD134 and PD-1 T-cells in SLE patients are increased in SLE. The aim of this study was to characterize CD134 and PD-1CD4 T-cells according to their ability to produce IFN-γ, IL-21 and IL-22 in SLE patients. METHODS:Peripheral blood of 39 SLE patients and 19 healthy controls (HC) was stimulated with phorbol myristate acetate (PMA) calcium ionophore (Ca-Io). The expression of IFN-γ, IL-21 and IL-22 T-cells within the CD134 and PD-1 T-cells was analyzed by flow cytometry. Disease activity was assessed by SLE Disease Activity Index. RESULTS:Peripheral unstimulated CD134 and PD-1 CD4 T-cells were significantly increased in patients with lupus nephritis. Upon stimulation both, CD134 and PD-1 CD4 T-cells, produced significantly less IFN-γ in SLE patients as compared to HC. The percentages of IL-22 within the CD134CD4 T-cells were also significantly decreased in SLE as compared to HC. CONCLUSION:CD134 and PD-1CD4 T-cells have mainly a Th1 effector T-cell signature. A lower proportion produces also IL-21 and IL-22. The impaired capacity to produce IFN-γ and IL-22 in SLE patients may contribute to the pathogenesis of the disease. 10.1186/s40001-019-0385-6

Association of interleukin 22 gene polymorphisms and serum IL-22 level with risk of systemic lupus erythematosus in a Chinese population. Clinical and experimental immunology The aim of this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of the interleukin 22 (IL-22) gene and systemic lupus erythematosus (SLE) in a Chinese population. Three IL-22 SNPs (rs2227485, rs2227513 and rs2227491) were genotyped using SNaPshot SNP genotyping assays and identified by sequencing in 314 SLE patients and 411 healthy controls. The IL-22 level of serum was assessed by enzyme-linked immunosorbent assay (ELISA) kits. Data were analysed by spss version 17.0 software. We found that rs2227513 was associated with an increased risk of SLE [AG versus AA: adjusted odds ratio (aOR) = 2·24, 95% confidence interval (CI) = 1·22-4·12, P = 0·010; G versus· A: adjusted OR = 2·18, 95% CI = 1·20-3·97, P = 0·011]. Further analysis in patients with SLE showed that the AG genotype and G allele were associated with an increased risk of renal disorder in SLE (G versus A: aOR = 3·09, 95% CI = 1·30-7·33, P = 0·011; AG versus· AA: aOR = 3·25, 95% CI = 1·35-7·85, P = 0·009). In addition, the concentration of IL-22 was significantly lower in the rs2227513 AG genotype compared with AA genotype (P = 0·028). These results suggest that rs2227513 polymorphism might contribute to SLE susceptibility, probably by decreasing the expression of IL-22. 10.1111/cei.13133