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

Lanfen Chen, Zhangguo Chen, Kristi Baker, Elizabeth M Halvorsen, Andre Pires da Cunha, Magdalena B Flak, Georg Gerber, Yu-Hwa Huang, Shuhei Hosomi, Janelle C Arthur, Ken J Dery, Takashi Nagaishi, Nicole Beauchemin, Kathryn V Holmes, Joshua W K Ho, John E Shively, Christian Jobin, Andrew B Onderdonk, Lynn Bry, Howard L WeinerDarren E Higgins, Richard S Blumberg

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)930-46
Number of pages17
JournalImmunity
Volume37
Issue number5
DOIs
Publication statusPublished - 16 Nov 2012

Keywords

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

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