P-selectin glycoprotein ligand-1 in T cells.
OBJECTIVE
We review P-selectin glycoprotein ligand-1 (PSGL-1) as a selectin and chemokine-binding adhesion molecule. PSGL-1 is widely studied in neutrophils. Here, we focus on T cells, because PSGL-1 was recently described as a major immunomodulatory molecule during viral infection. PSGL-1 also plays a crucial role in T-cell homeostasis by binding to lymphoid chemokines, and can induce tolerance by enhancing the functions of regulatory T cells.


RESULTS
PSGL-1 was originally described as a leukocyte ligand for P-selectin, but it is actually a ligand for all selectins (P-, L- and E-selectin), binds chemokines, activates integrins and profoundly affects T-cell biology. It has been shown recently that PSGL-1 can modulate T cells during viral infection by acting as a negative regulator for T-cell functions. Absence of PSGL-1 promotes effector CD4 and CD8 T-cell differentiation and prevents T-cell exhaustion. Consistent with this, tumor growth was significantly reduced in PSGL-1-deficient mice because of an enhanced number of effector T cells together with reduced levels of inhibitory receptors that induce T-cell exhaustion.


CONCLUSIONS
PSGL-1 is the best-studied selectin ligand and has become a posterchild of versatility in leukocyte adhesion, inflammation and immunology. The direct involvement of PSGL-1 in T-cell biology suggests that it might be a drug target. Indeed, PSGL-1 has been tested in some clinical trials and recently, PSGL-1 blockers were proposed as a potential cotherapy in cancer immunotherapy.
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Michael
M
Abadier
Klaus
K
Ley
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D016023:Integrins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D019087:Selectins / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D018925:Chemokines; D016023:Integrins; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D019087:Selectins