Interleukin (IL)‐10 plays a key role in controlling intestinal inflammation. IL‐10‐deficient mice and patients with mutations in IL‐10 or its receptor, IL‐10R, show increased susceptibility to inflammatory bowel diseases (IBD). Protein tyrosine phosphatase, non‐receptor type 22 (PTPN22) controls immune cell activation and the equilibrium between regulatory and effector T cells, playing an important role in controlling immune homoeostasis of the gut. Here, we examined the role of PTPN22 in intestinal inflammation of IL‐10‐deficient (IL‐10–/–) mice. We crossed IL‐10–/– mice with PTPN22–/– mice to generate PTPN22–/–IL‐10–/– double knock‐out mice and induced colitis with dextran sodium sulphate (DSS). In line with previous reports, DSS‐induced acute and chronic colitis was exacerbated in IL‐10–/– mice compared to wild‐type (WT) controls. However, PTPN22–/–IL‐10–/– double knock‐out mice developed milder disease compared to IL‐10–/– mice. IL‐17‐promoting innate cytokines and T helper type 17 (Th17) cells were markedly increased in PTPN22–/–IL‐10–/– mice, but did not provide a protctive function. CXCL1/KC was also increased in PTPN22–/–IL‐10–/– mice, but therapeutic injection of CXCL1/KC in IL‐10–/– mice did not ameliorate colitis. These results show that PTPN22 promotes intestinal inflammation in IL‐10‐deficient mice, suggesting that therapeutic targeting of PTPN22 might be beneficial in patients with IBD and mutations in IL‐10 and IL‐10R.
Clinical & Experimental Immunology – Wiley
Published: Sep 1, 2019
Keywords: ; ; ;
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