The Short Isoform of the CEACAM1 Receptor in Intestinal T Cells Regulates Mucosal Immunity and Homeostasis via Tfh Cell Induction

SummaryCarcinoembryonic 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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (232 K)Download as PowerPoint slideHighlights► Intestinal T cells predominately express CEACAM1-S rather than CEACAM1-L ► Independent of CEACAM1-L, CEACAM1-S acts as a costimulatory molecule in T cells ► CEACAM1-S on specific T cell subsets drives secretory IgA production by B cells ► CEACAM1 regulates commensal microbiota and host resistance to intestinal pathogens