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Int J Clin Exp Pathol. 2014 Jan 15;7(2):509-20. eCollection 2014.

Tim-1-Fc suppresses chronic cardiac allograft rejection and vasculopathy by reducing IL-17 production.

Author information

  • 1Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University Shanghai, China.
  • 2National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University Shanghai, China.
  • 3Department of Pharmacology, 411 Naval Medical Hospital Shanghai, China.
  • 4The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.

Abstract

Previously, we demonstrated that Tim-1-Fc prevents acute cardiac graft rejection by inhibiting Th1 response. In the present report, we tackled the impact of Tim-1-Fc on Th17 cells in a model of cardiac chronic rejection. Administration of Tim-1-Fc did not result in a detectable impact on innate immunity and regulatory T cells, while it provided protection for Bm12-derive cardiac grafts against chronic rejection in B6 recipients, as manifested by the reduction of inflammatory infiltration along with less severity of vasculopathy. Studies in T-bet(-/-) recipients by implanting Bm12-derived cardiac grafts further revealed that Tim-1-Fc significantly protected cardiac grafts from chronic rejection along with attenuated production of IL-17 producing T cells. Depletion of CD4 and CD8 T cells or blockade of IL-17 in T-bet(-/-) recipients demonstrated that Tim-1-Fc selectively suppresses Th17 differentiation along with attenuated IL-17 secretion. Together, our data suggest that Tim-1-Fc protects cardiac grafts from chronic rejection by suppressing CD4 Th17 development and functionality. Therefore, Tim-1-Fc might be a potential immunosuppressive agent in the setting of cardiac transplantation.

KEYWORDS:

Th17; Tim-1; vasculopathy

PMID:
24551271
PMCID:
PMC3925895
[PubMed - indexed for MEDLINE]
Free PMC Article
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