Heme Oxygenase-1 Ameliorates Dextran Sulfate Sodium-induced Acute Murine Colitis by Regulating Th17/Treg Cell Balance [Immunology]

August 11th, 2014 by Zhang, L., Zhang, Y., Zhong, W., Di, C., Lin, X., Xia, Z.

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD) is a group of autoimmune diseases characterized by non-specific inflammation in the gastrointestinal tract. Recent investigations suggest that activation of Th17 cells and/or deficiency of regulatory T cells (Treg) is involved in the pathogenesis of IBD. Heme oxygenase (HO) -1 is a protein with a wide range of anti-inflammatory and immune-regulatory function, which exerts significantly protective roles in various T cell-mediated diseases. In this study, we aim to explore the immunological regulation of HO-1 in the dextran sulfate sodium (DSS)-induced model of experimental murine colitis. BALB/c mice were administered 4% DSS orally; some mice were intraperitoneally pretreated with HO-1 inducer hemin or HO-1 inhibitor Sn-protoporphyrin IX (SnPP). The results show that hemin enhances the colonic expression of HO-1 and significantly ameliorates the symptoms of colitis with improved histological changes, accompanied by a decreased proportion of Th17 cells and increased number of Tregs in mesenteric lymph node (MLN) and spleen. Moreover, induction of HO-1 down-regulates retinoic acid-related orphan receptor γt (RORγt) expression and IL-17A levels, while promoting Treg-related forkhead box p3 (Foxp3) expression and IL-10 levels in colon. Further study in vitro revealed that up-regulated HO-1 switched the naive T cells to Tregs when cultured under a Th17-inducing environment, which involved in IL-6R blockade. Therefore, HO-1 may exhibit anti-inflammatory activity in the murine model of acute experimental colitis via regulating the balance between Th17 and Treg cells, thus providing a possible novel therapeutic target in IBD.