Research ArticleBARRIER IMMUNITY

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

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Science Translational Medicine  04 Dec 2019:
Vol. 11, Issue 521, eaaw8718
DOI: 10.1126/scitranslmed.aaw8718

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Tissue-resident T cells evade eviction

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.

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+ 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.

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