A CD103 + Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis.

Autor:	Clemente-Casares X; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada., Hosseinzadeh S; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, M5S 1A1, Canada., Barbu I; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada; Department of Immunology, University of Toronto, Toronto ON, M5S 1A1, Canada., Dick SA; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada., Macklin JA; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, M5S 1A1, Canada., Wang Y; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada., Momen A; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada., Kantores C; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada., Aronoff L; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, M5S 1A1, Canada., Farno M; AgroParisTech, Paris, France., Lucas TM; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Avery J; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Zarrin-Khat D; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada; Ted Rogers Centre for Heart Research, Toronto ON, M5G 1L7, Canada., Elsaesser HJ; Princess Margaret Cancer Center, Immune Therapy Program, UHN, Toronto ON, M5G 1L7, Canada., Razani B; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Lavine KJ; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA., Husain M; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, M5S 1A1, Canada; Peter Munk Cardiac Centre, Toronto ON, M5G 1L7, Canada; Ted Rogers Centre for Heart Research, Toronto ON, M5G 1L7, Canada., Brooks DG; Department of Immunology, University of Toronto, Toronto ON, M5S 1A1, Canada; Princess Margaret Cancer Center, Immune Therapy Program, UHN, Toronto ON, M5G 1L7, Canada., Robbins CS; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, M5S 1A1, Canada; Department of Immunology, University of Toronto, Toronto ON, M5S 1A1, Canada; Peter Munk Cardiac Centre, Toronto ON, M5G 1L7, Canada., Cybulsky M; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, M5S 1A1, Canada., Epelman S; Toronto General Hospital Research Institute, University Health Network (UHN), Toronto ON, M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, M5S 1A1, Canada; Department of Immunology, University of Toronto, Toronto ON, M5S 1A1, Canada; Peter Munk Cardiac Centre, Toronto ON, M5G 1L7, Canada; Ted Rogers Centre for Heart Research, Toronto ON, M5G 1L7, Canada. Electronic address: slava.epelman@uhn.ca.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2017 Nov 21; Vol. 47 (5), pp. 974-989.e8.
DOI:	10.1016/j.immuni.2017.10.011
Abstrakt:	Innate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identities and functions remain poorly defined. We utilized a combination of genetic fate mapping, parabiotic, transcriptional, and functional analyses and demonstrated that the heart contained two major conventional dendritic cell (cDC) subsets, CD103 + and CD11b + , which differentially relied on local proliferation and precursor recruitment to maintain their tissue residency. Following viral infection of the myocardium, cDCs accumulated in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages. cDC depletion abrogated antigen-specific CD8 + T cell proliferative expansion, transforming subclinical cardiac injury to overt heart failure. These effects were mediated by CD103 + cDCs, which are dependent on the transcription factor BATF3 for their development. Collectively, our findings identified resident cardiac cDC subsets, defined their origins, and revealed an essential role for CD103 + cDCs in antigen-specific T cell responses during subclinical viral myocarditis. (Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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