Premium
Hyperlipidemia Promotes Anti‐Donor Th17 Responses That Accelerate Allograft Rejection
Author(s) -
Yuan J.,
Bagley J.,
Iacomini J.
Publication year - 2015
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13350
Subject(s) - medicine , hyperlipidemia , immunology , endocrinology , diabetes mellitus
Hyperlipidemia occurs in 95% of organ transplant recipients, however its effect on organ allograft rejection has not been investigated. We found that induction of hyperlipidemia in mice caused a significant acceleration of rejection of cardiac allografts. Accelerated rejection was associated with an aggressive T cell infiltrate that mediated significant tissue damage as well as increased serum levels of the proinflammatory cytokines IL‐2, IL‐6, and IL‐17. Hyperlipidemic mice had an increased number of Th17 cells in their periphery and rejecting allografts from hyperlipidemic mice contained significant numbers of IL‐17 producing T cells that were not detectable in transplants harvested from controls. Neutralization or genetic ablation of IL‐17 prolonged survival of cardiac allografts transplanted into hyperlipidemic recipients, suggesting that IL‐17 production promotes accelerated rejection. Analysis of alloreactive T cell frequencies directly ex vivo in naïve mice revealed that the frequency of donor reactive IL‐17 producing cells in hyperlipidemic was increased prior to antigen exposure, suggesting that hyperlipidemia was sufficient to alter T cell alloreactivity and promote anti‐donor Th17 responses on first exposure to antigen. Together, our data suggest that hyperlipidemia alters rejection by altering the types of T cell subsets that respond to donor antigen by promoting Th17 biased anti‐donor reactivity.