Bifidobacterium longum alleviates dextran sulfate sodium-induced colitis by suppressing IL-17A response: Involvement of intestinal epithelial costimulatory molecules

Although some bacterial strains show potential to prevent colitis, their mechanisms are not fully understood. Here, we investigated the anti-colitic mechanisms of Bifidobacterium longum subsp. infantis JCM 1222^T, focusing on the relationship between interleukin (IL)-17A secreting CD4 ⁺ T cells and intestinal epithelial costimulatory molecules in mice. Oral administration of JCM 1222^T to mice alleviated dextran sulfate sodium (DSS)-induced acute colitis. The expression of type 1 helper T (Th1)- and IL-17 producing helper T (Th17)-specific cytokines and transcriptional factors was suppressed by JCM 1222^T treatment. Intestinal epithelial cells (IECs) from colitic mice induced IL-17A production from CD4⁺ T cells in a cell-cell contact-dependent manner, and this was suppressed by oral treatment with JCM 1222^T. Using blocking antibodies for costimulatory molecules, we revealed that epithelial costimulatory molecules including CD80 and CD40, which were highly expressed in IECs from colitic mice, were involved in IEC-induced IL-17A response. Treatment of mice and intestinal epithelial cell line Colon-26 cells with JCM 1222^T decreased the expression of CD80 and CD40. Collectively, these data indicate that JCM 1222^T negatively regulate epithelial costimulatory molecules, and this effect might be attributed, at least in part, to suppression of IL-17A in DSS-induced colitis.