Short, but Smart: SCFAs Train T Cells in the Gut to Fight Autoimmunity in the Brain

Abstract

In this issue of Immunity, Haghikia and colleagues (2015) demonstrate that dietary fatty acids, by modulating gut microbes and their metabolism, regulate mucosal immune cells to impact systemic immunity. Using this mechanism, dietary and bacteria-derived medium-chain and long-chain fatty acids exacerbate, whereas short-chain fatty acids ameliorate, autoimmunity in the brain.

Figure 1. Gut Fatty Acids Drive Intestinal T Cell Differentiation that Influences Development of Autoimmunity in other Distal Tissues

Naive CD4⁺ T cells that originate in the bone marrow and thymus migrate to the lamina propria of the gut, where they differentiate into various T helper subtypes under the influence of fatty acids derived from the diet or bacteria. In the presence of MCFAs or LCFAs, T cell differentiation is skewed toward inflammatory subtypes (Th1 and Th17), whereas in the presence of SCFAs, differentiation is skewed toward regulatory subtypes (Treg cells). These fatty-acid-influenced T cells drive pathogenic or protective responses in other tissues such as the central nervous system and modulate autoimmunity. Abbreviations are as follows: MCFAs, medium-chain fatty acids; LCFAs, long-chain fatty acids; SCFAs, short-chain fatty acids.