Davis, Amanda S. Woodward and Roozen, Hayley N. and Dufort, Matthew J. and DeBerg, Hannah A. and Delaney, Martha A. and Mair, Florian and Erickson, Jami R. and Slichter, Chloe K. and Berkson, Julia D. and Klock, Alexis M. and Mack, Matthias and Lwo, Yu and Ko, Alexander and Brand, Rhonda M. and McGowan, Ian and Linsley, Peter S. and Dixon, Douglas R. and Prlic, Martin (2019) The human tissue-resident CCR5(+) T cell compartment maintains protective and functional properties during inflammation. SCIENCE TRANSLATIONAL MEDICINE, 11 (521): eaaw8718. ISSN 1946-6234, 1946-6242
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MARAVIROC; BLOCKADE; IMMUNITY; EXPRESSION; MECHANISM; EFFICACY; S1P(1); |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2020 09:35 |
| Last Modified: | 20 Mar 2020 09:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25693 |
Actions (login required)
 |
View Item |
