期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 205, 期 13, 页码 3145-3158出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20081661
关键词
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资金
- National Institutes of Health [HL070295]
- National Institutes of Health Medical Scientist Training [5T32GM07205]
Interleukin (IL) 1 alpha produced by human endothelial cells (ECs), in response to tumor necrosis factor (TNF) or to co-culture with allogeneic T cells in a TNF-dependent manner, can augment the release of cytokines from alloreactive memory T cells in vitro. In a human mouse chimeric model of artery allograft rejection, ECs lining the transplanted human arteries express IL-1 alpha, and blocking IL-1 reduces the extent of human T cell infiltration into the artery intima and selectively inhibits IL-17 production by infiltrating T cells. In human skin grafts implanted on immunodeficient mice, administration of IL-17 is sufficient to induce mild inflammation. In cultured cells, IL-17 acts preferentially on vascular smooth muscle cells rather than ECs to enhance production of proinflammatory mediators, including IL-6, CXCL8, and CCL20. Neutralization of IL-17 does not reduce T cell infiltration into allogeneic human artery grafts, but markedly reduces IL-6, CXCL8, and CCL20 expression and selectively inhibits CCR6(+) T cell accumulation in rejecting arteries. We conclude that graft-derived IL-1 can promote T cell intimal recruitment and IL-17 production during human artery allograft rejection, and suggest that targeting IL-1 in the perioperative transplant period may modulate host alloreactivity.
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