Endothelial Cell-Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production.
Circulation
; 141(6): 464-478, 2020 02 11.
Article
en En
| MEDLINE
| ID: mdl-31744330
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-1hiICOS+CCR2+CXCR5-) displaying features of recently described 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, a clinical manifestation of IRI, these cells were Ki-67+IL-18R1+ and could be expanded ex vivo in response to IL-18.CONCLUSIONS:
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Inmunoglobulina M
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Daño por Reperfusión
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Trasplante de Órganos
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Linfocitos T Colaboradores-Inductores
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Interleucina-18
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Células Endoteliales de la Vena Umbilical Humana
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Isoanticuerpos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Circulation
Año:
2020
Tipo del documento:
Article