Short chain fatty acids regulation of neutrophil production of IL-10

Abstract

Abstract Despite questions regarding the role of microbiota in regulation of host immune responses within the intestines, evidence suggests that in the context of disease and autoimmunity bacterial metabolites might impact the systemic immune response. Otherwise indigestible carbohydrates are metabolized into short-chain fatty acids (SCFAs) by gut bacteria. SCFAs have been shown to inhibit intestinal inflammation in experimental colitis through regulation of mucosal T cells and macrophages. Recently, neutrophils have been shown to regulate intestinal homeostasis and the pathogenesis of IBD, however, how SCFAs may regulate neutrophil function is unclear. In this study, we demonstrate that SCFA differentially regulate neutrophil cytokine production. Of the three major SCFAs butyrate, acetate, and propionate, only butyrate down-regulated neutrophil IL-10 production. We further showed that butyrate-inhibition of neutrophil IL-10 is independent of GPR43, in that butyrate also inhibited IL-10 production in GPR43 deficient neutrophils. We recently showed that IL-23 induced neutrophil production of IL-17 and IL-22 in a mTOR dependent manner; however, butyrate did not affect IL-23-induced IL-17 and IL-22 production in neutrophils. Taken together, our data indicates that microbiota metabolites differentially regulate neutrophil cytokine production.