Circulating integrin α4β7+ CD4 T cells are enriched for proliferative transcriptional programs in HIV infection,FEBS Letters

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Circulating integrin α4β7+ CD4 T cells are enriched for proliferative transcriptional programs in HIV infection
FEBS Letters ( IF 3.0 ) Pub Date : 2021-07-19 , DOI: 10.1002/1873-3468.14163
Yashavanth S Lakshmanappa ₁ , Jamin W Roh _{1,

2} , Niharika N Rane ₁ , Ashok R Dinasarapu ₃ , Daphne D Tran ₁ , Vijayakumar Velu _{4,

5} , Anandi N Sheth _{6,

7} , Igho Ofotokun _{6,

7} , Rama R Amara _{5,

8} , Colleen F Kelley ₉ , Elaine Waetjen ₁₀ , Smita S Iyer _{1,

11,

12}

Affiliation

Center for Immunology and Infectious Diseases, UC Davis, CA, USA.
Graduate Group in Immunology, UC Davis, CA, USA.
Department of Human Genetics, Emory University, Atlanta, GA, USA.
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory Vaccine Center, Emory University, Atlanta, GA, USA.
Grady Infectious Diseases Program, Grady Health System, Atlanta, GA, USA.
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
Division of Infectious Diseases, Department of Medicine, The Hope Clinic of the Emory Vaccine Research Center, Emory University School of Medicine, Decatur, GA, USA.
Department of Obstetrics and Gynecology, UC Davis School of Medicine, CA, USA.
California National Primate Research Center, UC Davis, CA, USA.
Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, UC Davis, CA, USA.

HIV preferentially infects α₄β₇⁺ CD4 T cells, forming latent reservoirs that contribute to HIV persistence during antiretroviral therapy. However, the properties of α₄β₇⁺ CD4 T cells in blood and mucosal compartments remain understudied. Employing two distinct models of HIV infection, HIV-infected humans and simian–human immunodeficiency virus (SHIV)-infected rhesus macaques, we show that α₄β₇⁺ CD4 T cells in blood are enriched for genes regulating cell cycle progression and cellular metabolism. Unlike their circulating counterparts, rectal α₄β₇⁺ CD4 T cells exhibited a core tissue-residency gene expression program. These features were conserved across primate species, indicating that the environment influences memory T-cell transcriptional networks. Our findings provide an important molecular foundation for understanding the role of α₄β₇ in HIV infection.

中文翻译：

循环整合素 α4β7+ CD4 T 细胞在 HIV 感染中富集增殖转录程序

HIV 优先感染 α ₄ β ₇⁺ CD4 T 细胞，形成潜在的病毒库，在抗逆转录病毒治疗期间导致 HIV 持续存在。然而，血液和粘膜区室中α ₄ β ₇⁺ CD4 T 细胞的特性仍未得到充分研究。采用两种不同的 HIV 感染模型，HIV 感染的人类和猿猴-人类免疫缺陷病毒 (SHIV) 感染的恒河猴，我们表明血液中的 α 4 β 7 ₊ CD4 _T^细胞富含调节细胞周期进程和细胞代谢的基因. 与循环对应物不同，直肠 α ₄ β ₇⁺CD4 T 细胞表现出核心组织驻留基因表达程序。这些特征在灵长类物种中是保守的，表明环境影响记忆 T 细胞转录网络。_{我们的研究结果为理解 α 4} β ₇在 HIV 感染中的作用提供了重要的分子基础。

更新日期：2021-09-13

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