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

Chen L, Chen Z, Baker K, Halvorsen EM, da Cunha AP, Flak MB, Gerber G, Huang YH, Hosomi S, Arthur JC, Dery KJ, Nagaishi T, Beauchemin N, Holmes KV, Ho JW, Shively JE, Jobin C, Onderdonk AB, Bry L, Weiner HL, Higgins DE, Blumberg RS.

Citation

Chen L, Chen Z, Baker K, Halvorsen EM, da Cunha AP, Flak MB, Gerber G, Huang YH, Hosomi S, Arthur JC, Dery KJ, Nagaishi T, Beauchemin N, Holmes KV, Ho JW, Shively JE, Jobin C, Onderdonk AB, Bry L, Weiner HL, Higgins DE, Blumberg RS. (2012) The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction. Immunity 37(5):930-946.

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.