黏膜归巢自然杀伤细胞与 HIV 感染者的衰老有关。

Mucosal-homing natural killer cells are associated with aging in persons living with HIV.

机构信息

Division of Innate and Comparative Immunology, Center for Human Systems Immunology, Duke University, Durham, NC, USA; Department of Surgery, Duke University, Durham, NC, USA.

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.

出版信息

Cell Rep Med. 2022 Oct 18;3(10):100773. doi: 10.1016/j.xcrm.2022.100773. Epub 2022 Oct 7.

Natural killer (NK) cells are critical modulators of HIV transmission and disease. Recent evidence suggests a loss of NK cell cytotoxicity during aging, yet analysis of NK cell biology and aging in people with HIV (PWH) is lacking. Herein, we perform comprehensive analyses of people aging with and without HIV to determine age-related NK phenotypic changes. Utilizing high-dimensional flow cytometry, we analyze 30 immune-related proteins on peripheral NK cells from healthy donors, PWH with viral suppression, and viremic PWH. NK cell phenotypes are dynamic across aging but change significantly in HIV and on antiretroviral drug therapy (ART). NK cells in healthy aging show increasing ⍺4β7 and decreasing CCR7 expression and a reverse phenomenon in PWH. These HIV-associated trafficking patterns could be due to NK cell recruitment to HIV reservoir formation in lymphoid tissue or failed mucosal signaling in the HIV-infected gut but appear to be tight delineators of age-related NK cell changes.

自然杀伤 (NK) 细胞是 HIV 传播和疾病的关键调节剂。最近的证据表明，NK 细胞的细胞毒性在衰老过程中丧失，但对 HIV 感染者 (PWH) 的 NK 细胞生物学和衰老进行分析的研究还很缺乏。在此，我们对伴有和不伴有 HIV 的人群进行了全面的分析，以确定与年龄相关的 NK 表型变化。利用高维流式细胞术，我们分析了来自健康供体、病毒抑制的 PWH 和病毒血症的 PWH 的外周 NK 细胞上的 30 种免疫相关蛋白。NK 细胞表型在衰老过程中是动态变化的，但在 HIV 感染和抗逆转录病毒药物治疗 (ART) 中会发生显著变化。健康衰老的 NK 细胞表现出 ⍺4β7 表达增加和 CCR7 表达减少，而 PWH 则出现相反的现象。这些与 HIV 相关的趋化模式可能是由于 NK 细胞被招募到淋巴组织中的 HIV 储存库形成，或者是由于 HIV 感染肠道中黏膜信号传导失败所致，但它们似乎是与年龄相关的 NK 细胞变化的明确区分标志。