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CD 1d‐mediated lipid presentation by CD 11c + cells regulates intestinal homeostasis
Author(s) -
Sáez de Guinoa Julia,
Jimeno Rebeca,
Gaya Mauro,
Kipling David,
Garzón María José,
DunnWalters Deborah,
Ubeda Carles,
Barral Patricia
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797537
Subject(s) - library science , humanities , art , computer science
Intestinal homeostasis relies on a continuous dialogue between the commensal bacteria and the immune system. Natural killer T ( NKT ) cells, which recognize CD 1d‐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 CD 11c + cells (including dendritic cells ( DC s) and macrophages) are essential to mediate lipid presentation within the gut ultimately controlling intestinal NKT cell homeostasis and activation. Conversely, CD 1d 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 CD 1d expression on DC /macrophage populations as mice with conditional deletion of CD 1d on CD 11c + cells exhibit dysbiosis and altered immune homeostasis. These results unveil the importance of CD 11c + 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.