ICOS ligand and IL-10 synergize to promote host–microbiota mutualism

Abstract

Significance Both IL10 and ICOSL are risk alleles for inflammatory bowel disease (IBD). The role of IL-10 in preventing gut inflammation is well established experimentally and clinically. However, it is unclear whether and how ICOSL functions in the intestines, and how it might impact susceptibility to gut inflammation. We found that in mice, the absence of ICOSL is associated with increased accumulation of IL-10–producing CD4 T cells but dramatic reductions in anti-commensal antibodies, resulting in limited recognition of antigens implicated in the progression of IBD. Simultaneous disruption of both pathways, either genetically or transiently, resulted in colitis. Therefore, we have identified an IBD-relevant axis in intestinal immune regulation predicated on the cooperative functions of ICOSL and CD4 T cell–derived IL-10.