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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 The EMBO Journal, 37 (5), e97537. pp. 1-17.

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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
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Sáez de Guinoa, Julia
Jimeno, Rebeca
Gaya, Mauro
Kipling, David
Garzón, María José
Ubeda, Carles
Barral, Patricia
Date : 2018
Funders : Medical Research Council (MRC)
DOI : 10.15252/embj.201797537
Copyright Disclaimer : © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords : CD1d; Microbiota; NKT cell
Depositing User : Clive Harris
Date Deposited : 16 Jan 2018 14:10
Last Modified : 11 Dec 2018 11:23

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