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Cell. 2017 Nov 2;171(4):783-794.e13. doi: 10.1016/j.cell.2017.08.046. Epub 2017 Sep 21.

Intestinal Epithelial and Intraepithelial T Cell Crosstalk Mediates a Dynamic Response to Infection.

Author information

1
Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA; Laboratory of Translational Immunology, University Medical Center Utrecht, 3584 CX, Utrecht, the Netherlands.
2
Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA. Electronic address: breis@rockefeller.edu.
3
Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
4
Departments of Orofacial Sciences and Pediatrics, Institute of Human Genetics and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA 94143, USA.
5
Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY 10065, USA.
6
Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA. Electronic address: mucida@rockefeller.edu.

Abstract

Intestinal intraepithelial lymphocytes (IELs) are located at the critical interface between the intestinal lumen, which is chronically exposed to food and microbes, and the core of the body. Using high-resolution microscopy techniques and intersectional genetic tools, we investigated the nature of IEL responses to luminal microbes. We observed that TCRγδ IELs exhibit unique microbiota-dependent location and movement patterns in the epithelial compartment. This behavioral pattern quickly changes upon exposure to different enteric pathogens, resulting in increased interepithelial cell (EC) scanning, expression of antimicrobial genes, and glycolysis. Both dynamic and metabolic changes to γδ IEL depend on pathogen sensing by ECs. Direct modulation of glycolysis is sufficient to change γδ IEL behavior and susceptibility to early pathogen invasion. Our results uncover a coordinated EC-IEL response to enteric infections that modulates lymphocyte energy utilization and dynamics and supports maintenance of the intestinal epithelial barrier. VIDEO ABSTRACT.

KEYWORDS:

IELs; gammadelta glycolysis; intestine; lymphocytes; microbiota; mucosal imaging; multiphoton; myd88

PMID:
28942917
PMCID:
PMC5670000
DOI:
10.1016/j.cell.2017.08.046
[Indexed for MEDLINE]
Free PMC Article

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