CD1d-mediated lipid presentation by CD11c+cells regulates intestinal homeostasis.
Sáez de Guinoa J, Jimeno R, Gaya M, Kipling D, Garzón MJ, Dunn-Walters D, Ubeda C, Barral P
EMBO J. Mar 2018
COMMENT: The composition of the intestinal microbiota varies significantly between individuals, and evidence suggests that alterations in the populations of commensal bacteria (dysbiosis) can result in susceptibility to multiple pathological conditions including inflammatory bowel disease, obesity and diabetes. The intestinal immune system has unique features to control the expansion and composition of intestinal microbes without triggering inflammation.
Intestinal homeostasis relies on a continuous dialogue between the commensal bacteria and the intestinal immune system. Many factors contribute to the control of the intestinal microbiota composition, including familial transmission and diet, but also genetics. For instance, MHC polymorphisms can significantly alter intestinal microbial communities, suggesting that specific T‐cell recognition of commensal‐derived antigens strongly contributes to the establishment of intestinal homeostasis. Natural killer T (NKT) cells, which recognize CD1d-restricted microbial lipids and self-lipids, contribute to the regulation of mucosal immunity, yet the mechanisms underlying their functions remain poorly understood.
In this study, Saez de Guinoa et al. demonstrate that NKT cells respond to intestinal lipids and CD11c+cells (including dendritic cells (DCs) and macrophages) are essential to mediate lipid presentation within the gut ultimately controlling intestinal NKT cell homeostasis and activation. Conversely, CD1d and NKT cells participate in the control of the intestinal bacteria composition and compartmentalization, in the regulation of the IgA repertoire and in the induction of regulatory T cells within the gut. These changes in intestinal homeostasis require CD1d expression on DC/macrophage populations as mice with conditional deletion of CD1d on CD11c+cells exhibit dysbiosis and altered immune homeostasis.
These results unveil the importance of CD11c+cells in controlling lipid-dependent immunity in the intestinal compartment and reveal an NKT cell-DC crosstalk as a key mechanism for the regulation of gut homeostasis.