Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production
Authors' conclusion
IRI promotes elaboration of IL-18 from endothelial cells to selectively expand alloreactive IL-18R1+ T peripheral helper cells in allograft tissues to promote donor-specific antibody formation.
Study context
- Population
- Ischemia reperfusion injury in allografts; patients with delayed graft function
- Outcome
- Mechanism linking IRI to donor-specific antibodies: endothelial cell-derived IL-18 and expansion of T peripheral helper cells
Methodological detailshumanized models, patient specimens
- Humanized models
- Patient specimens
Main finding
As reported in the abstract
- Ischemia reperfusion injury (IRI) induces immunoglobulin M-dependent complement activation on endothelial cells, assembling an NLRP3 inflammasome via a Rab5-ZFYVE21-NIK axis
- Upregulation of ICOS-L and PD-L2 on endothelial cells
- Endothelial cell-derived IL-18 selectively expands a T-cell population (CD4+CD45RO+PD-1hiICOS+CCR2+CXCR5-) with features of T peripheral helper cells
- This population highly expressed IL-18R1 and promoted donor-specific antibodies in response to IL-18 in vivo
- In patients with delayed graft function, these cells were Ki-67+IL-18R1+ and could be expanded ex vivo in response to IL-18
Original publication
Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production. Circulation. Published 20 November 2019. doi:10.
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