Soluble DC-HIL/Gpnmb Modulates T-Lymphocyte Extravasation to Inflamed Skin

Vijay Ramani, Jin-Sung Chung, Kiyoshi Ariizumi, Ponciano D. Cruz

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Previously, we discovered antigen-presenting cells to express DC-HIL receptor and to secrete its soluble form (soluble DC-HIL [sDC-HIL]), both of which bind to syndecan-4 on T cells and endothelial cells (ECs), with the former binding attenuating T-cell function and the latter binding promoting angiogenesis. In this study, we examined the effects of sDC-HIL binding to EC on T-cell extravasation using an allergic contact dermatitis model in mice. The hapten oxazolone applied to ear skin in sensitized mice upregulated cutaneous expression of sDC-HIL, which downregulated the allergic reaction by reducing transendothelial migration of T cells but not other immune cells (neutrophils and mast cells). Moreover, intravenously infused sDC-HIL bound to EC in blood vessels of oxazolone-challenged skin in a scattered and patchy pattern, and intravital microscopic analysis revealed that blood-circulating T cells firmly adhere to DC-HIL–treated endothelia. This regulatory property of sDC-HIL requires syndecan-4 expression by both EC and T cells. Our findings indicate that the DC-HIL/syndecan-4 pathway mediates a cross-talk between T cells and ECs, regulating the cutaneous immune response by preventing extravasation of activated T cells into inflamed skin.

Original languageEnglish (US)
JournalJournal of Investigative Dermatology
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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