The human tissue-resident CCR5 + T cell compartment maintains protective and functional properties during inflammation.

Autor: Woodward Davis AS; Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA 98109, USA., Roozen HN; Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA 98109, USA., Dufort MJ; Systems Immunology Division, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA., DeBerg HA; Systems Immunology Division, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA., Delaney MA; Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA., Mair F; Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA 98109, USA., Erickson JR; Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA 98109, USA., Slichter CK; Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA 98109, USA.; Department of Global Health, University of Washington, Seattle, WA 98195, USA., Berkson JD; Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA 98109, USA., Klock AM; Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA., Mack M; Department of Internal Medicine-Nephrology, University Hospital Regensburg, 93053 Regensburg, Germany., Lwo Y; Department of Periodontics, University of Washington, Seattle, WA 98195, USA., Ko A; Department of Periodontics, University of Washington, Seattle, WA 98195, USA., Brand RM; Department of Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.; Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA., McGowan I; University of Miami Miller School of Medicine, Miami, FL 33136, USA.; Orion Biotechnology, Ottawa, ON, K1S 1N4, Canada., Linsley PS; Systems Immunology Division, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA., Dixon DR; Department of Periodontics, University of Washington, Seattle, WA 98195, USA., Prlic M; Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA 98109, USA. mprlic@fredhutch.org.; Department of Global Health, University of Washington, Seattle, WA 98195, USA.; Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2019 Dec 04; Vol. 11 (521).
DOI: 10.1126/scitranslmed.aaw8718
Abstrakt: CCR5 is thought to play a central role in orchestrating migration of cells in response to inflammation. CCR5 antagonists can reduce inflammatory disease processes, which has led to an increased interest in using CCR5 antagonists in a wide range of inflammation-driven diseases. Paradoxically, these antagonists appear to function without negatively affecting host immunity at barrier sites. We reasoned that the resolution to this paradox may lie in the CCR5 + T cell populations that permanently reside in tissues. We used a single-cell analysis approach to examine the human CCR5 + T cell compartment in the blood, healthy, and inflamed mucosal tissues to resolve these seemingly contradictory observations. We found that 65% of the CD4 tissue-resident memory T (TRM) cell compartment expressed CCR5. These CCR5 + T RM cells were enriched in and near the epithelial layer and not only limited to T H 1-type cells but also contained a large T H 17-producing and a stable regulatory T cell population. The CCR5 + T RM compartment was stably maintained even in inflamed tissues including the preservation of T H 17 and regulatory T cell populations. Further, using tissues from the CHARM-03 clinical trial, we found that CCR5 + T RM are preserved in human mucosal tissue during treatment with the CCR5 antagonist Maraviroc. Our data suggest that the human CCR5 + T RM compartment is functionally and spatially equipped to maintain barrier immunity even in the absence of CCR5-mediated, de novo T cell recruitment from the periphery.
(Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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