Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4⁺ T cells.

ABSTRACT:

Introduction

Ischemia reperfusion injury (IRI) confers worsened outcomes and is an increasing clinical problem in solid organ transplantation. Previously, we identified a "Ptch^Hi" T-cell subset that selectively received costimulatory signals from endothelial cell-derived Hedgehog (Hh) morphogens to mediate IRI-induced vascular inflammation.

Methods

Here, we used multi-omics approaches and developed a humanized mouse model to resolve functional and migratory heterogeneity within the PtchHi population.

Results

Hh-mediated costimulation induced oligoclonal and polyclonal expansion of clones within the PtchHi population, and we visualized three distinct subsets within inflamed, IRI-treated human skin xenografts exhibiting polyfunctional cytokine responses. One

SUBMITTER: Wang S 

PROVIDER: S-EPMC10616247 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature