Short-chain fatty acids inhibit the activation of T lymphocytes and myeloid cells and induce innate immune tolerance

Abstract The intestinal microbiota contributes to gut immune homeostasis, where short-chain fatty acids (SCFAs) function as the major mediators. We aimed elucidate immunomodulatory effects of acetate, propionate, and butyrate. With that in mind, we sought characterise expression SCFA receptors transporters well SCFAs’ impact on activation different cells. Whereas all three SCFAs decreased tumour necrosis factor (TNF)-α production activated T cells, only butyrate propionate inhibited interferon (IFN)-γ, interleukin (IL)-17, IL-13, IL-10 production. Butyrate chemokine CCR9 CCR10 T- B-cells, respectively. Similarly, were effective inhibitors IL-1β, IL-6, TNF-α, myeloid cells upon lipopolysaccharide R848 stimulation. Acetate was less efficient at inhibiting cytokine except for IFN-α. Moreover, IL-6 TNF-α monocytes, dendritic (mDC), plasmacytoid (pDC), whereas acetate relatively more prominent pDCs. In monocytes mDCs, a inhibitor, but it equally pDCs activation. also studied ability induce trained immunity or tolerance. – not prevented Toll-like receptor-mediated SCFA-trained demonstrated by reduced TNF-α. Our findings indicate are adaptive innate response did immunity. may be explained differential receptor transporter profiles