CD1d-mediated lipid presentation by CD11c+ cells regulates intestinal homeostasis
Por:
Sáez de Guinoa J, Jimeno R, Gaya M, Kipling D, Garzón MJ, Dunn-Walters D, Ubeda C and Barral P
Publicada:
1 mar 2018
Ahead of Print:
29 ene 2018
Resumen:
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.
Filiaciones:
Sáez de Guinoa J:
The Peter Gorer Department of Immunobiology, King's College London, London, UK
The Francis Crick Institute, London, UK
Jimeno R:
The Peter Gorer Department of Immunobiology, King's College London, London, UK
The Francis Crick Institute, London, UK
Gaya M:
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
Kipling D:
Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK
:
Departamento de Genómica y Salud, Centro Superior de Investigación en Salud Pública - FISABIO, Valencia, Spain
Dunn-Walters D:
Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
:
Departamento de Genómica y Salud, Centro Superior de Investigación en Salud Pública - FISABIO, Valencia, Spain
Centers of Biomedical Research Network (CIBER) in Epidemiology and Public Health, Madrid, Spain
Barral P:
The Francis Crick Institute, London, UK
Green Published, Green Accepted, hybrid
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