Gut CD4+ T cells are incompletely restored in most HIV-1-infected individuals on antiretroviral therapy, notably Th17 cells, a key subset in mucosal homeostasis. By contrast, gut Th22 cells are usually restored at normal frequencies. Th22 cells display a CCR6+CCR10+ phenotype and could thus respond to CCL20- and CCL28-mediated chemotaxis, while Th17 cells, which express CCR6 but not CCR10, depend on CCL20. Herein, we found that CCL28 is normally expressed by duodenal enterocytes of treated HIV-1-infected individuals, while CCL20 expression is blunted. Ex vivo, we showed that Th22 cells contribute to the reduction of CCL20 production by enterocytes through an IL-22- and IL-18-dependent mechanism. Th22 cells preferentially migrate via CCL20- rather than CCL28-mediated chemotaxis when both chemokines are available in the microenvironment. However, when the CCL20/CCL28 ratio drops, as in treated HIV-1-infected individuals, Th22 cells can migrate via the CCR10-CCL28 axis, as an alternative to CCR6-CCL20. This could explain the better reconstitution of gut Th22 compared with Th17 cells on antiretroviral therapy. Lastly, we assessed the relationships between the frequencies of gut Th17 and Th22 cells and inflammatory markers related to microbial translocation, and showed that Th22 cells do not compensate for the loss of Th17 cells in treated HIV-1-infected individuals.

中文翻译：

---

Th22 细胞被 CCL28 在肠道中有效地募集，作为 CCL20 的替代品，但不能补偿接受治疗的 HIV-1 感染个体中 Th17 细胞的损失。

大多数接受抗逆转录病毒治疗的 HIV-1 感染者的肠道 CD4+ T 细胞未完全恢复，尤其是 Th17 细胞，它是粘膜稳态的关键亚群。相比之下，肠道 Th22 细胞通常以正常频率恢复。Th22 细胞显示出 CCR6+CCR10+ 表型，因此可以响应 CCL20 和 CCL28 介导的趋化性，而表达 CCR6 但不表达 CCR10 的 Th17 细胞依赖于 CCL20。在此，我们发现 CCL28 通常由接受治疗的 HIV-1 感染个体的十二指肠肠细胞表达，而 CCL20 表达减弱。在体外，我们发现 Th22 细胞通过 IL-22 和 IL-18 依赖性机制有助于减少肠细胞产生的 CCL20。当两种趋化因子在微环境中可用时，Th22 细胞优先通过 CCL20 而非 CCL28 介导的趋化性迁移。然而，当 CCL20/CCL28 比率下降时，如在接受治疗的 HIV-1 感染个体中，Th22 细胞可以通过 CCR10-CCL28 轴迁移，作为 CCR6-CCL20 的替代品。这可以解释在抗逆转录病毒治疗中，与 Th17 细胞相比，肠道 Th22 细胞的重建效果更好。最后，我们评估了肠道 Th17 和 Th22 细胞的频率与微生物易位相关的炎症标志物之间的关系，并表明 Th22 细胞不能补偿接受治疗的 HIV-1 感染个体中 Th17 细胞的损失。