Primed T cell responses to chemokines are regulated by the immunoglobulin-like molecule CD31.
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.
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Madhav
M
Kishore
Liang
L
Ma
Georgina
G
Cornish
Sussan
S
Nourshargh
Federica M
FM
Marelli-Berg
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D005260:Female; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D064413:3-Phosphoinositide-Dependent Protein Kinases; D018925:Chemokines; D007136:Immunoglobulins; D019869:Phosphatidylinositol 3-Kinases; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt