期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 214, 期 11, 页码 3311-3329出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20161791
关键词
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资金
- National Institutes of Health [NIH R01 HL123658, NIH 1KL2TR001063-01, NIH R01HL131831, NIH T32 HL 69770, NIH T32AI007077-34]
- American Heart Association [AHA GIA 13GRNT 14560068]
Despite emerging data indicating a role for T cells in profibrotic cardiac repair and healing after ischemia, little is known about whether T cells directly impact cardiac fibroblasts (CFBs) to promote cardiac fibrosis (CF) in nonischemic heart failure (HF). Recently, we reported increased T cell infiltration in the fibrotic myocardium of nonischemic HF patients, as well as the protection from CF and HF in TCR-alpha(-/-) mice. Here, we report that T cells activated in such a context are mainly IFN-gamma(+), adhere to CFB, and induce their transition into myofibroblasts. Th1 effector cells selectively drive CF both in vitro and in vivo, whereas adoptive transfer of Th1 cells, opposite to activated IFN-gamma(-/-) Th cells, partially reconstituted CF and HF in TCR-alpha(-/-) recipient mice. Mechanistically, Th1 cells use integrin alpha 4 to adhere to and induce TGF-beta in CFB in an IFN-gamma-dependent manner. Our findings identify a previously unrecognized role for Th1 cells as integrators of perivascular CF and cardiac dysfunction in nonischemic HF.
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