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CD1d‐mediated lipid presentation by CD11c+ cells regulates intestinal homeostasis

Sáez de Guinoa, Julia, Jimeno, Rebeca, Gaya, Mauro, Kipling, David, Garzón, María José, Dunn-Walters, Deborah, Ubeda, Carles and Barral, Patricia 2018. CD1d‐mediated lipid presentation by CD11c+ cells regulates intestinal homeostasis. EMBO Journal 37 (5) , e97537. 10.15252/embj.201797537

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: European Molecular Biology Organization; Nature Publishing Group
ISSN: 0261-4189
Date of First Compliant Deposit: 9 March 2018
Date of Acceptance: 22 December 2017
Last Modified: 12 Mar 2018 14:10
URI: http://orca.cf.ac.uk/id/eprint/109786

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