The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction

Immunity. 2012 Nov 16;37(5):930-46. doi: 10.1016/j.immuni.2012.07.016. Epub 2012 Nov 1.

Abstract

Carcinoembryonic antigen cell adhesion molecule like I (CEACAM1) is expressed on activated T cells and signals through either a long (L) cytoplasmic tail containing immune receptor tyrosine based inhibitory motifs, which provide inhibitory function, or a short (S) cytoplasmic tail with an unknown role. Previous studies on peripheral T cells show that CEACAM1-L isoforms predominate with little to no detectable CEACAM1-S isoforms in mouse and human. We show here that this was not the case in tissue resident T cells of intestines and gut associated lymphoid tissues, which demonstrated predominant expression of CEACAM1-S isoforms relative to CEACAM1-L isoforms in human and mouse. This tissue resident predominance of CEACAM1-S expression was determined by the intestinal environment where it served a stimulatory function leading to the regulation of T cell subsets associated with the generation of secretory IgA immunity, the regulation of mucosal commensalism, and defense of the barrier against enteropathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Amino Acid Motifs / immunology
  • Animals
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / immunology*
  • Carcinoembryonic Antigen / metabolism
  • Cytoplasm / genetics
  • Cytoplasm / immunology
  • Cytoplasm / metabolism
  • Homeostasis
  • Immunity, Mucosal / genetics
  • Immunity, Mucosal / immunology*
  • Immunoglobulin A / genetics
  • Immunoglobulin A / immunology
  • Immunoglobulin A / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / immunology*
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology
  • Lymphocyte Activation
  • Metagenome / immunology
  • Mice
  • Mice, Inbred C57BL
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Protein Isoforms
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tyrosine / genetics
  • Tyrosine / immunology
  • Tyrosine / metabolism

Substances

  • Carcinoembryonic Antigen
  • Ceacam1 protein, mouse
  • Immunoglobulin A
  • NFATC Transcription Factors
  • Protein Isoforms
  • Receptors, Immunologic
  • Tyrosine