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_H1-type cells but also contained a large T_H17-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_H17 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.

据认为，CCR5在协调细胞对炎症的反应中起着重要作用。CCR5拮抗剂可以减少炎症性疾病的进程，这导致人们越来越广泛地将CCR5拮抗剂用于各种炎症驱动的疾病。矛盾的是，这些拮抗剂似乎起作用而对屏障位点的宿主免疫没有负面影响。我们认为，解决这一矛盾的方法可能在于永久存在于组织中的CCR5 ⁺ T细胞群体。我们使用单细胞分析方法来检查人类CCR5 ⁺血液，健康和粘膜组织中的T细胞区室解决了这些看似矛盾的观察结果。我们发现65％的CD4组织驻留记忆T（TRM）细胞区室表达CCR5。这些CCR5 ⁺ Ť _RM细胞和上皮细胞层附近富集和不仅不限于T _ħ 1型细胞，也含有大T _ħ 17产生和稳定的调节性T细胞群。即使在发炎的组织中，包括保存T _H 17和调节性T细胞，CCR5 ⁺ T _RM隔室也可以稳定保持。此外，使用CHARM-03临床试验的组织，我们发现CCR5 ⁺ T在用CCR5拮抗剂Maraviroc治疗期间，_RM被保留在人的粘膜组织中。我们的数据表明，即使在没有CCR5介导的新生T细胞从外周募集的情况下，人CCR5 ⁺ T _RM区室在功能和空间上也能保持屏障免疫力。