title: Dedicated immunosensing of the mouse intestinal epithelium facilitated by a pair of genetically coupled lectin-like receptors.
abstract: 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.
authors.affiliation: Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Leibelt
authors.affiliation: Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: M E
authors.initials: ME
authors.lastname: Friede
authors.affiliation: Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rohe
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Gütle
authors.affiliation: Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Rutkowski
authors.affiliation: Institute for Biochemistry I, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Weigert
authors.affiliation: Department of Immunology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway.
authors.forename: L
authors.initials: L
authors.lastname: Kveberg
authors.affiliation: Department of Immunology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway.
authors.forename: J T
authors.initials: JT
authors.lastname: Vaage
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: M W
authors.initials: MW
authors.lastname: Hornef
authors.affiliation: Institute for Molecular Medicine, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Steinle
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D005810:Multigene Family; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D011070:Poly I-C / Q000494:pharmacology; D011485:Protein Binding; D055503:Protein Multimerization; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011948:Receptors, Antigen, T-Cell; D011070:Poly I-C