Dedicated immunosensing of the mouse intestinal epithelium facilitated by a pair of genetically coupled lectin-like receptors

The integrity of the intestinal epithelium is constantly surveyed by a peculiar subset of innate-like T lymphocytes embedded in the epithelial cell layer, hence called intestinal intraepithelial lymphocytes (IELs). IELs are thought to act as “first-line” sentinels sensing the state of adjacent epith...

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Bibliographic Details
Published in:	Mucosal immunology Vol. 8; no. 2; pp. 232 - 242
Main Authors:	Leibelt, S, Friede, M E, Rohe, C, Gütle, D, Rutkowski, E, Weigert, A, Kveberg, L, Vaage, J T, Hornef, M W, Steinle, A
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-03-2015 Elsevier Limited
Subjects:	631/250/2152/1566/1572 631/250/347 Allergology Animals Antibodies Biomedical and Life Sciences Biomedicine Cell Line Epithelial Cells - drug effects Epithelial Cells - metabolism Female Gastroenterology Gene Expression Humans Immunology Immunophenotyping Intestinal Mucosa - drug effects Intestinal Mucosa - immunology Intestinal Mucosa - metabolism Lectins, C-Type - chemistry Lectins, C-Type - genetics Lectins, C-Type - metabolism Lymphocytes - immunology Lymphocytes - metabolism Mice Multigene Family NK Cell Lectin-Like Receptor Subfamily B - genetics NK Cell Lectin-Like Receptor Subfamily B - metabolism Organ Specificity - genetics Peyer's Patches - cytology Peyer's Patches - immunology Peyer's Patches - metabolism Phenotype Poly I-C - pharmacology Protein Binding Protein Multimerization Receptors, Antigen, T-Cell - metabolism T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism
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Summary:	The integrity of the intestinal epithelium is constantly surveyed by a peculiar subset of innate-like T lymphocytes embedded in the epithelial cell layer, hence called intestinal intraepithelial lymphocytes (IELs). IELs are thought to act as “first-line” sentinels sensing the state of adjacent epithelial cells via both T-cell receptors and auxiliary receptors. Auxiliary receptors modulating IEL activity include C-type lectin-like receptors encoded in the natural killer gene complex such as NKG2D. Here, we report that the CTLR Nkrp1g is expressed by a subpopulation of mouse CD103 + IELs allowing immunosensing of the intestinal epithelium through ligation of the genetically coupled CTLR Clr-f that is almost exclusively expressed on differentiated intestinal epithelial cells (IECs). Most of these Nkrp1g-expressing IELs exhibit a γδTCR bright Nkg2a − phenotype and are intimately associated with the intestinal epithelium. As Clr-f expression strongly inhibits effector functions of Nkrp1g-expressing cells and is upregulated upon poly(I:C) challenge, Clr-f molecules may quench reactivity of these IELs towards the epithelial barrier that is constantly provoked by microbial and antigenic stimuli. Altogether, we here newly characterize a genetically linked C-type lectin-like receptor/ligand pair with a highly restricted tissue expression that apparently evolved to allow for a dedicated immunosurveillance of the mouse intestinal epithelium.
ISSN:	1933-0219 1935-3456
DOI:	10.1038/mi.2014.60