Anti-IL22 monoclonal antibody, clone 6H9

Interleukin (IL) 17-producing T helper (Th17) cells play critical roles in the clearance of extracellular bacteria and fungi as well as the pathogenesis of various autoimmune diseases, such as multiple sclerosis, psoriasis, and ulcerative colitis. Although a global transcriptional regulatory network of Th17 cell differentiation has been mapped recently, the participation of epigenetic modifications in the differentiation process has yet to be elucidated. We demonstrated here that histone H3 lysine-27 (H3K27) demethylation, predominantly mediated by the H3K27 demethylase Jmjd3, crucially regulated Th17 cell differentiation. Activation of naive CD4 1 T cells immediately induced high expression of Jmjd3. Genetic depletion of Jmjd3 in CD4 1 T cells specifically impaired Th17 cell differentiation both in vitro and in vivo. Ectopic expression of Jmjd3 largely rescued the impaired differentiation of Th17 cells in vitro in Jmjd3-deficientCD4(+) T cells. Importantly, Jmjd3-deficient mice were resistant to the induction of experimental autoimmune encephalomyelitis (EAE). Furthermore, inhibition of the H3K27 demethylase activity with the specific inhibitor GSK-J4 dramatically suppressed Th17 cell differentiation in vitro. At the molecular level, Jmjd3 directly bound to and reduced the level of H3K27 trimethylation (me3) at the genomic sites of Rorc, which encodes the master Th17 transcription factor Ror gamma t, and Th17 cytokine genes such as Il17, Il17f, and Il22. Therefore, our studies established a critical role of Jmjd3-mediated H3K27 demethylation in Th17 cell differentiation and suggest that Jmjd3 can be a novel therapeutic target for suppressing autoimmune responses.

Aim of the work: To analyze the level of interleukin 22 (IL-22) in sera of systemic lupus erythematosus (SLE) patients and to associate its level to disease activity, skin involvement and lupus nephritis. Patients and methods: The study included 70 SLE patients under treatment with diseasemodifying antirheumatic drugs and in 50 age and sex matched healthy controls. Patients were assessed for clinical and laboratory variables including the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Antinuclear Antibodies (ANA), and anti-double stranded deoxyribonucleic acid (ds-DNA). The SLE disease activity index (SLEDAI) was evaluated. Level of IL22 in patients and controls sera was investigated by ELISA. Results: The 70 patients were 64 women and 6 men with a mean age of 27.2 +/- 8.2 years. Levels of IL-22 were significantly increased in sera of SLE patients compared to controls (median 162 pg/mL and 58 pg/mL, respectively; p < 0.001). IL-22 significantly correlated with the SLEDAI as well as with ESR and CRP (r = 0.41 and p = 0.016; r = 0.42 and p = 0.01; r = 0.996 and p < 0.001, respectively). IL-22 level revealed a significant association with skin involvement (p < 0.001) and with the absence of lupus nephritis (p = 0.007). Conclusion: Our data suggest that increased serum IL-22 may contribute to the pathogenesis of SLE. Its elevated serum level allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in SLE. IL22 in serum seems to be a significant index reflecting skin and renal involvement in SLE. (C) 2016 Publishing services provided by Elsevier B.V. on behalf of Egyptian Society of Rheumatic Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).