AUTHOR=Hertati Ai , Hayashi Shusaku , Ogawa Yudai , Yamamoto Takeshi , Kadowaki Makoto TITLE=Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.573470 DOI=10.3389/fphar.2020.573470 ISSN=1663-9812 ABSTRACT=

Disturbance of epithelial barrier function causes chronic intestinal inflammation such as inflammatory bowel disease. Several studies have reported that Th2 cytokines such as interleukin (IL)-4 and IL-13 play an important role in the regulation of intestinal barrier function. However, the precise role of the IL-4 receptor α subunit (IL-4Rα) in intestinal inflammation remains unclear. Thus, we used an experimental colitis model to investigate the role of IL-4Rα in intestinal inflammation. IL-4Rα-deficient (IL-4Rα-/-) mice and their littermate wild-type (WT) mice were used. Experimental colitis was induced by administration of 3% dextran sulfate sodium (DSS) in the drinking water for seven days. Treatment with DSS caused body weight loss, an increase in the disease activity index and histological abnormalities in WT colitis mice, all of which were significantly attenuated in IL-4Rα-/- colitis mice. Neutrophil infiltration in the colonic mucosa was reduced in IL-4Rα-/- colitis mice compared with WT colitis mice. NADPH oxidase 1 expression and reactive oxygen species production were increased in the colons of IL-4Rα-/- mice. Furthermore, elevated intestinal permeability induced by DSS treatment was suppressed in IL-4Rα-/- colitis mice. These results demonstrate that IL-4Rα-/- mice exhibit reduced susceptibility to DSS-induced colitis. Our present findings suggest that IL-4Rα deficiency enhances intestinal mucosal barrier function through the upregulation of NADPH oxidase 1-dependent reactive oxygen species production, thereby suppressing the development of intestinal inflammation.