Microvesicles derived from activated T cells promote human mast cell migration via the S1P1 receptor

J Leukoc Biol. 2025 Aug 5;117(8):qiaf111. doi: 10.1093/jleuko/qiaf111.

Abstract

Morphologic studies show increased mast cell activation during T-cell-mediated inflammation. Previous research demonstrated that microvesicles from activated T cells, but not from resting T cells, stimulate human mast cells via the MAPK pathway, leading to degranulation and cytokine release. This study investigates whether microvesicles derived from activated T cells also promote mast cell migration. Microvesicles were isolated from activated or resting T-cell supernatants, and mast cell migration was measured using a transwell assay. The molecular mechanisms were analyzed with specific inhibitors. Results showed that microvesicles derived from activated T cells significantly enhanced human mast cell chemotaxis, which depended on ERK and p38 phosphorylation but not on PI3 K. In addition, migration was mediated by the S1P1 receptor rather than S1P2 and by sphingosine kinase 1, indicating a role of S1P1 in mast cell migration induced by microvesicles derived from activated T cells. In summary, microvesicles derived from activated T cells act as chemoattractants, guiding mast cells to inflammatory sites where they become activated, highlighting their importance in T-cell-mediated inflammation.

Keywords: T cells; mast cells; microvesicles; migration.

MeSH terms

  • Cell Movement*
  • Cell-Derived Microparticles* / immunology
  • Chemotaxis
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Lymphocyte Activation* / immunology
  • Mast Cells* / cytology
  • Mast Cells* / immunology
  • Mast Cells* / physiology
  • Phosphorylation
  • Receptors, Lysosphingolipid* / metabolism
  • Receptors, Lysosphingolipid* / physiology
  • Sphingosine-1-Phosphate Receptors
  • T-Lymphocytes* / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Receptors, Lysosphingolipid
  • p38 Mitogen-Activated Protein Kinases
  • S1PR1 protein, human
  • Sphingosine-1-Phosphate Receptors
  • Extracellular Signal-Regulated MAP Kinases