Butyrate and propionate regulated proliferation and activation of human group–2 innate lymphoid cells (ILC2s)

Abstract

Commensal intestinal microbiota are thought to play fundamental roles in the induction, training and regulation of the human immune system, at least in part through innumerable microbial products such as short-chain fatty acids (SCFAs). We hypothesized that SCFAs such as butyrate, propionate and acetate directly affect group-2 innate lymphoid cell (ILC2) functions and regulate allergic inflammation. To test this hypothesis, we determined the effects of SCFAs on human ILC2s in vitro. Human ILC2s were sorted from peripheral blood lymphocytes (PBMC) of healthy donors and expanded in the presence of feeder cells and recombinant IL-2 for 3-4 weeks. After confirming their purity, the ILC2s were cultured with IL-2 and IL-33 in the presence and absence of such SCFAs as butyrate, propionate and acetate. Then the cells’ viability, proliferation and cytokine/chemokine production were determined. We found that butyrate and propionate suppressed the ILC2s’ production of such type 2 cytokines/chemokine as IL-5, IL-9, IL-13 and IL-8 . Butyrate and propionate also induced apoptosis and suppressed proliferation of the cells through downregulation of IL-2Rα. Conversely, acetate showed none of those effects on the cells. Butyrate and propionate, but not acetate, produced by the intestinal microbiota may play important roles in regulating the proliferation activation and cytokine/chemokine production profiles of ILC2s, thereby leading to regulation of allergic inflammatory diseases.