PT  - JOURNAL ARTICLE
AU  - Woodward Davis, Amanda S.
AU  - Roozen, Hayley N.
AU  - Dufort, Matthew J.
AU  - DeBerg, Hannah A.
AU  - Delaney, Martha A.
AU  - Mair, Florian
AU  - Erickson, Jami R.
AU  - Slichter, Chloe K.
AU  - Berkson, Julia D.
AU  - Klock, Alexis M.
AU  - Mack, Matthias
AU  - Lwo, Yu
AU  - Ko, Alexander
AU  - Brand, Rhonda M.
AU  - McGowan, Ian
AU  - Linsley, Peter S.
AU  - Dixon, Douglas R.
AU  - Prlic, Martin
TI  - The human tissue-resident CCR5<sup>+</sup> T cell compartment maintains protective and functional properties during inflammation
AID  - 10.1126/scitranslmed.aaw8718
DP  - 2019 Dec 04
TA  - Science Translational Medicine
PG  - eaaw8718
VI  - 11
IP  - 521
4099  - http://stm.sciencemag.org/content/11/521/eaaw8718.short
4100  - http://stm.sciencemag.org/content/11/521/eaaw8718.full
AB  - CCR5 antagonism, explored in various disease settings, does not appear to disrupt barrier immunity. Woodward Davis et al. examined human oral mucosa to characterize CCR5+ T cells in healthy and inflamed tissues. These cells were present below the epithelia and accumulated during inflammation. They had a range of phenotypes, including TH1, TH17, and regulatory cells. Rectal biopsies from a clinical trial using a CCR5 antagonist revealed that CCR5+ T cells were retained even during treatment. These data show that tissue residency may not be perturbed by CCR5 antagonism, allowing barrier immunity to remain intact.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+ TRM cells were enriched in and near the epithelial layer and not only limited to TH1-type cells but also contained a large TH17-producing and a stable regulatory T cell population. The CCR5+ TRM compartment was stably maintained even in inflamed tissues including the preservation of TH17 and regulatory T cell populations. Further, using tissues from the CHARM-03 clinical trial, we found that CCR5+ TRM are preserved in human mucosal tissue during treatment with the CCR5 antagonist Maraviroc. Our data suggest that the human CCR5+ TRM 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.