Liver X receptor regulates Th17 and RORγt+ Treg cells by distinct mechanisms.

Mucosal Immunology
Sara Martina ParigiEduardo J. Villablanca

Abstract

The gastrointestinal microenvironment, dominated by dietary compounds and the commensal bacteria, is a major driver of intestinal CD4+ T helper (Th) cell differentiation. Dietary compounds can be sensed by nuclear receptors (NRs) that consequently exert pleiotropic effects including immune modulation. Here, we found that under homeostatic conditions the NR Liver X receptor (LXR), a sensor of cholesterol metabolites, regulates RORγt+ CD4 T cells in the intestine draining mesenteric lymph node (MLN). While LXR activation led to a decrease, LXR-deficiency resulted in an increase in MLN Th17 and RORγt+ Tregs. Mechanistically, LXR signaling in CD11c+ myeloid cells was required to control RORγt+ Treg. By contrast, modulation of MLN Th17 was independent of LXR signaling in either immune or epithelial cells. Of note, horizontal transfer of microbiota between LXRα-/- and WT mice was sufficient to only partially increase MLN Th17 in WT mice. Despite LXRα deficiency resulted in an increased abundance of Ruminococcaceae and Lachnospiraceae bacterial families compared to littermate controls, microbiota ablation (including SFB) was not sufficient to dampen LXRα-mediated expansion of MLN Th17. Altogether, our results suggest that LXR modulate...Continue Reading

References

May 3, 2002·Journal of Medicinal Chemistry·Jon L CollinsTimothy M Willson
Feb 18, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Daniel WalcherNikolaus Marx
Mar 3, 2006·The Journal of Clinical Investigation·Noam Zelcer, Peter Tontonoz
Jun 27, 2007·The Journal of Experimental Medicine·Michele L CatonBoris Reizis
Oct 20, 2009·Cell·Ivaylo I IvanovDan R Littman
Jan 27, 2011·The Journal of Clinical Investigation·Guoliang CuiYing Qin Zang
Sep 28, 2012·Genome Biology·Xochitl C MorganCurtis Huttenhower
Feb 15, 2013·Immunological Reviews·Matthew ShaleFiona Powrie
Aug 28, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hajime TakeuchiMakoto Iwata
Sep 23, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Soraya TalebZiad Mallat
Dec 18, 2015·Nature·Jakob von MoltkeRichard M Locksley
Mar 7, 2017·Immune Network·Hiroko Nagao-Kitamoto, Nobuhiko Kamada
Nov 10, 2017·Frontiers in Immunology·Jan KempskiSamuel Huber
Nov 17, 2017·Nature·Nicola WilckDominik N Müller
Dec 13, 2017·European Journal of Immunology·Stefanie Ascher, Christoph Reinhardt
Jan 11, 2018·Scientific Reports·Sara M ParigiEduardo J Villablanca
Jan 18, 2018·Cell·Masoud F TavazoieSohail F Tavazoie
Jan 27, 2018·Journal of Autoimmunity·Theodora AgaliotiNicola Gagliani
Jul 20, 2018·Lipids in Health and Disease·Baoning LiuEnqi Liu
Nov 28, 2018·Nature Reviews. Gastroenterology & Hepatology·Alexander R MoschenTim Raine
Aug 6, 2019·Frontiers in Microbiology·Alessandra Lo PrestiMichele Pier Luca Guarino
Feb 29, 2020·Reproductive Toxicology·Oscar E DiazEduardo J Villablanca

❮ Previous
Next ❯

Citations

May 20, 2021·Proceedings of the National Academy of Sciences of the United States of America·Kirsty E WaddingtonInés Pineda-Torra

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
scRNAseq
IECs
IEC
FACS

Software Mentioned

GraphPad Prism
UMAP

Related Concepts

Related Feeds

Related Papers

BioRxiv : the Preprint Server for Biology
Sara Martina ParigiEduardo J. Villablanca
The Journal of Immunology : Official Journal of the American Association of Immunologists
Mingming SunYingzi Cong
© 2021 Meta ULC. All rights reserved