美国麻省大学医学院Jeremy Luban团队发现，人类免疫缺陷病毒（HIV-1）诱导的细胞因子消耗了体内天然淋巴样细胞并促使TCF7依赖的记忆NK细胞扩增。相关论文在线发表在2020年2月17日出版的《自然-免疫学》杂志上。

在两个独立的实验中，研究人员发现，即使进行了有效的抗逆转录病毒治疗，HIV-1患者的血液和肠道中先天淋巴样细胞（ILC）也被耗竭。ILC耗竭与肠道固有层中性粒细胞的浸润、1型干扰素激活、微生物易位性增加以及自然杀伤（NK）细胞导致的炎症状态有关，这种炎症状态具有WNT转录因子TCF7依赖记忆T细胞的典型特征和染色质结构。

在急性HIV-1感染过程中细胞因子升高，这与体外ILC和NK细胞异常相似。这些结果表明，与HIV-1感染相关的炎性细胞因子不可逆地破坏ILC。这导致肠道上皮完整性丧失、微生物的移位和记忆NK细胞的炎症潜能增加，并解释了HIV-1患者患有慢性炎症的原因。

研究人员表示，人类免疫缺陷病毒1（HIV-1）感染与炎症加剧、心血管疾病、癌症和其它并发症风险增加有关。尽管进行了抗逆转录病毒治疗，但这些疾病仍然存在。

附：英文原文

Title: HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7 -dependent memory NK cells

Author: Yetao Wang, Lawrence Lifshitz, Kyle Gellatly, Carol L. Vinton, Kathleen Busman-Sahay, Sean McCauley, Pranitha Vangala, Kyusik Kim, Alan Derr, Smita Jaiswal, Alper Kucukural, Patrick McDonel, Peter W. Hunt, Thomas Greenough, JeanMarie Houghton, Ma Somsouk, Jacob D. Estes, Jason M. Brenchley, Manuel Garber, Steven G. Deeks, Jeremy Luban

Issue&Volume: 2020-02-17

Abstract: Human immunodeficiency virus 1 (HIV-1) infection is associated with heightened inflammation and excess risk of cardiovascular disease, cancer and other complications. These pathologies persist despite antiretroviral therapy. In two independent cohorts, we found that innate lymphoid cells (ILCs) were depleted in the blood and gut of people with HIV-1, even with effective antiretroviral therapy. ILC depletion was associated with neutrophil infiltration of the gut lamina propria, type 1 interferon activation, increased microbial translocation and natural killer (NK) cell skewing towards an inflammatory state, with chromatin structure and phenotype typical of WNT transcription factor TCF7-dependent memory T cells. Cytokines that are elevated during acute HIV-1 infection reproduced the ILC and NK cell abnormalities ex vivo. These results show that inflammatory cytokines associated with HIV-1 infection irreversibly disrupt ILCs. This results in loss of gut epithelial integrity, microbial translocation and memory NK cells with heightened inflammatory potential, and explains the chronic inflammation in people with HIV-1.

DOI: 10.1038/s41590-020-0593-9

Source: https://www.nature.com/articles/s41590-020-0593-9