P-selectin glycoprotein ligand-1 in T cells

Curr Opin Hematol. 2017 May;24(3):265-273. doi: 10.1097/MOH.0000000000000331.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Chemokines / metabolism
  • Cytoskeleton / metabolism
  • Glycosylation
  • Humans
  • Immune Tolerance
  • Immunomodulation
  • Integrins / metabolism
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Membrane Microdomains / metabolism
  • Protein Binding
  • Protein Transport
  • Selectins / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • Chemokines
  • Integrins
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Selectins