Abstract
CD31, an immunoglobulin-like molecule expressed by leukocytes and endothelial cells, is thought to contribute to the physiological regulation T cell homeostasis due to the presence of two immunotyrosine-based inhibitory motifs in its cytoplasmic tail. Indeed, loss of CD31 expression leads to uncontrolled T cell-mediated inflammation in a variety of experimental models of disease and certain CD31 polymorphisms correlate with increased disease severity in human graft-versus-host disease and atherosclerosis. The molecular mechanisms underlying CD31-mediated regulation of T cell responses have not yet been clarified. We here show that CD31-mediated signals attenuate T cell chemokinesis both in vitro and in vivo. This effect selectively affects activated/memory T lymphocytes, in which CD31 is clustered on the cell membrane where it segregates to the leading edge. We provide evidence that this molecular segregation, which does not occur in naïve T lymphocytes, might lead to cis-CD31 engagement on the same membrane and subsequent interference with the chemokine-induced PI3K/Akt signalling pathway. We propose that CD31-mediated modulation of memory T cell chemokinesis is a key mechanism by which this molecule contributes to the homeostatic regulation of effector T cell immunity.
Highlights
CD31, or platelet endothelial cell adhesion molecule-1 (PECAM-1) is a member of the immunoglobulin gene superfamily expressed at high density at the lateral borders of endothelial cells and at a lower density on the surface of hematopoietic cells including T lymphocytes [1]
We show that CD31 signals attenuate T cell responses to chemokines, a previously unknown function of this immunoreceptor
This spatial distribution favours molecular interactions on the same cell membrane, which we propose as a mechanism inducing CD31 signalling in polarized, migrating T cells
Summary
CD31, or platelet endothelial cell adhesion molecule-1 (PECAM-1) is a member of the immunoglobulin gene superfamily expressed at high density at the lateral borders of endothelial cells and at a lower density on the surface of hematopoietic cells including T lymphocytes [1].CD31–deficient mice exhibit a very mild phenotype and have normal numbers of T cells [2]. Genetic deletion of CD31 leads to exaggerated disease severity in inducible experimental models of T cell-mediated inflammation, including experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA) [3,4], suggesting that CD31 signals play a functional regulatory role under conditions of immunological stress. Single nucleotide polymorphisms of CD31 encoding amino acid substitutions at positions affecting the binding site [6] and the intracellular ITIMs [7] are associated with increased severity of graft-versushost disease after hematopoietic stem cell transplantation [8,9,10,11,12] and atherosclerosis [7,13]. T cell-mediated inflammation contributes to the pathogenesis of both these conditions, the molecular mechanisms underlying this link are at present unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
