CD1d-mediated lipid presentation by CD11c+ cells regulates intestinal homeostasis
journal contributionposted on 14.09.2020, 10:02 by Julia Sáez de Guinoa, Rebeca Jimeno, Mauro Gaya, David Kipling, María José Garzón, Deborah Dunn-Walters, Carles Ubeda, Patricia Barral
Intestinal homeostasis relies on a continuous dialogue between the commensal bacteria and the immune system. 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. Here, we 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.
CD1dNKT cellmicrobiotaAnimalsAntigens, CD1dCD11c AntigenDendritic CellsDysbiosisGastrointestinal MicrobiomeImmunoglobulin AInterleukin-4Intestinal MucosaMacrophagesMembrane LipidsMiceMice, Inbred C57BLMice, KnockoutNatural Killer T-CellsT-Lymphocytes, RegulatoryBarral - secDevelopmental Biology06 Biological Sciences08 Information and Computing Sciences11 Medical and Health Sciences