IL-4 Receptor-Alpha Signalling of Intestinal Epithelial Cells, Smooth Muscle Cells, and Macrophages Plays a Redundant Role in Oxazolone Colitis

Abstract

A hallmark of ulcerative colitis is the chronic colonic inflammation, which is the result of a dysregulated intestinal mucosal immune response. Epithelial barrier disruption which allows the entry of microorganisms eventually leads to more aggressive inflammation and potentially the removal of the colon. We have previously shown that the T helper- (Th-) type 2 cytokines, Interleukin- (IL-) 4 and IL-13, mediate CD4+ T cell- or B cell-driven inflammation in the oxazolone-induced mouse model of ulcerative colitis. In contrast, mice deficient in the shared receptor of IL-4 and IL-13, IL-4 receptor-alpha (IL-4Rα), on all cells develop an exacerbated disease phenotype. This suggests that a regulatory role of IL-4Rα is required to protect against severe colitis. However, the cell populations responsible for regulating the severity of disease onset through IL-4Rα in colitis are yet to be identified. By deleting IL-4Rα on specific cell subsets shown to play a role in mediating colitis, we determined their role in a loss of function approach. Our data demonstrated that the loss of IL-4Rα signalling on intestinal epithelial cells, smooth muscle cells, and macrophages/neutrophils had no effect on alleviating the pathology associated with colitis. These results suggest that IL-4/IL-13 signalling through IL-4Rα on nonhematopoietic intestinal epithelial or smooth muscle cells and hematopoietic macrophage/neutrophils has a redundant role in driving acute oxazolone colitis.

Cell-intrinsic IL4R alpha independence of large intestinal RELMα+ Ym1+ macrophages

“…Attempts to address the importance of the IL4Rα in the context of large intestinal macrophages have been limited by the Cre driver employed to delete the IL4Rα from macrophages and the markers used to define the M2 phenotype. Thus, recent work using oxazaloneinduced colitis in IL4Rαfl.LysM cre mice demonstrated no change in total Arg-1 mRNA expression in the intestine post infection (10). However, no macrophage specific expression of M2 markers was reported and the interpretation of this data is confounded by the known inefficiencies in LysM cre mediated deletion of the IL4Rα on macrophages during inflammation (11).…”

Clinical and Morphological Analysis of Efficacy of Intraperitoneal Ozone Application in Experimental Colitis: Preclinical Randomized Experimental Study

“…ОИК моделировали в два этапа с помощью 3%го спиртового раствора оксазолона (4-этоксиметилен-2-фенил-2-оксазолин-5-он). Первый этап заключался в накожной сенсибилизации нанесением 675 мкл/кг на межлопаточную область, второй -в ректальном введении 675 мкл/кг в толстую кишку на глубину 7 см [12,13].…”

Comparative analysis of the effectiveness of local application of vitamin D3 and 5-aminosalicylic acid in experimental colitis

“…На первом этапе была проведена сенсибилизация путем нанесения на кожу области между лопаток 150 мкл 3%-го спиртового раствора оксазолона, на втором этапе вводили на глубину 7-8 см per rectum 150 мкл 3%-го спиртового раствора оксазолона (рис. 1) [20,21]. Для анестезии использовали Золетил-100 (Virbac Sante Animal, Франция) в дозе 20 мг/кг.…”