CD1d‐mediated lipid presentation by CD11c+ cells regulates intestinal homeostasis
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44318_2018_Article_BFEMBJ201797537.pdf
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Author(s)
Sáez de Guinoa, Julia
Jimeno, Rebeca
Gaya, Mauro
Kipling, David
Garzón, María J.
Dunn‐Walters, Deborah
Ubeda, Carles
Barral, Patricia
Date Issued
January 29, 2018
Journal
The EMBO Journal
Publisher
Nature Publishing Group UK
Citation
The EMBO Journal. 2018 Jan 29;37(5):EMBJ201797537
Version
Final published version
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.
MIT Department
Ragon Institute of MGH, MIT and Harvard
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.15252/embj.201797537
