Endothelial Cell-Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production.

ABSTRACT:

Background

Ischemia reperfusion injury (IRI) predisposes to the formation of donor-specific antibodies, a factor contributing to chronic rejection and late allograft loss.

Methods

We describe a mechanism underlying the correlative association between IRI and donor-specific antibodies by using humanized models and patient specimens.

Results

IRI induces immunoglobulin M-dependent complement activation on endothelial cells that assembles an NLRP3 (NOD-like receptor pyrin domain-containing protein 3) inflammasome via a Rab5-ZFYVE21-NIK axis and upregulates ICOS-L (inducible costimulator ligand) and PD-L2 (programmed death ligand 2). Endothelial cell-derived interleukin-18 (IL-18) selectively expands a T-cell population (CD4+CD45RO+PD-1^hiICOS+CCR2+CXCR5-) displa

SUBMITTER: Liu L 

PROVIDER: S-EPMC7035199 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature