Synergy between anti-commensal antibodies and IL-10 in gut homeostasis and disease

Abstract To limit immune responses to gut-resident microbes, mucus and the epithelial barrier physically separate host system from microbial communities. Immunoglobulin A (IgA) antibodies are known help regulate colonization functions of mucus-associated commensals. However, mechanisms whereby other isotypes, including IgG, interface with components promote tolerance MA microbes still being unraveled. Our lab previously showed that, in mice impaired production T-dependent (TD) anti-commensal antibodies, IgA- IgG-mediated recognition mucus-derived bacterial antigens is significantly reduced. Moreover, transient depletion IL-10-producing cells devoid TD resulted rapid onset colitis. Therefore, we hypothesized that synergize IL-10 homeostasis colon. Here, show relative wild type mice, there increased levels colonic CD4 T lacking both IgG IgA (Aicda −/−) but not only (Iga −/−). Additionally, severe colitis Aicda −/−but Iga −/−mice. Importantly, this developed despite elevated IgM colon layer Furthermore, observed −/−mice suggesting a potentially compensatory role for IgA. Collectively, our data suggest an important contribution combination IL-10, promoting border-dwelling microbes. R01 AI162736, R21 DK118386