@article{17d6269348654e4b94f8d750762baed1,
title = "Gut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection",
abstract = "The innate immune cells underlying mucosal inflammatory responses and damage during acute HIV-1 infection remain incompletely understood. Here, we report a Vδ2 subset of gut-homing γδ T cells with significantly upregulated Δ42PD1 (a PD1 isoform) in acute (\textasciitilde{}20\%) HIV-1 patients compared to chronic HIV-1 patients (\textasciitilde{}11\%) and healthy controls (\textasciitilde{}2\%). The frequency of Δ42PD1+Vδ2 cells correlates positively with plasma levels of pro-inflammatory cytokines and fatty-acid-binding protein before detectable lipopolysaccharide in acute patients. The expression of Δ42PD1 can be induced by in vitro HIV-1 infection and is accompanied by high co-expression of gut-homing receptors CCR9/CD103. To investigate the role of Δ42PD1+Vδ2 cells in vivo, they were adoptively transferred into autologous humanized mice, resulting in small intestinal inflammatory damage, probably due to the interaction of Δ42PD1 with its cognate receptor Toll-like receptor 4 (TLR4). In addition, blockade of Δ42PD1 or TLR4 successfully reduced the cytokine effect induced by Δ42PD1+Vδ2 cells in vitro, as well as the mucosal pathological effect in humanized mice. Our findings have therefore uncovered a Δ42PD1–TLR4 pathway exhibited by virus-induced gut-homing Vδ2 cells that may contribute to innate immune activation and intestinal pathogenesis during acute HIV-1 infection. Δ42PD1+Vδ2 cells may serve as a target for the investigation of diseases with mucosal inflammation.",
author = "Cheung, \{Allen Ka Loon\} and Kwok, \{Hau Yee\} and Yiru Huang and Min Chen and Yufei Mo and Xilin Wu and Lam, \{Ka Shing\} and Kong, \{Hoi Kuan\} and Lau, \{Terrence Chi Kong\} and Jingying Zhou and Jingjing Li and Lin Cheng and Lee, \{Boon Kiat\} and Qiaoli Peng and Xiaofan Lu and Minghui An and Hui Wang and Hong Shang and Boping Zhou and Hao Wu and Aimin Xu and Yuen, \{Kwok Yung\} and Zhiwei Chen",
note = "Funding Information: The authors thank K. Miyake for providing the MD2 plasmid, K.H. Kok for CFP, YFP and NF-κB-luciferase plasmids and C. Cheng-Mayer for critical discussions. The authors thank L. Liu for technical advice with immunohistochemical staining. The authors acknowledge the Faculty Core Facility of the LKS Faculty of Medicine, HKU, for technical assistance with confocal microscopy. This work was supported by research grants from the Hong Kong Research Grant Council (RGC: HKU5/CRF/13G, RGC17103514, RGC17122915 and A-HKU709/14 to Z.C.); the Health and Medical Research Fund (HMRF: 14130582 to Z.C., 15140372 to A.K.L.C.); the San-Ming Project of Medicine in Shenzhen (to Z.C. and H.Wa.); the National Science and Technology Major Project (2012ZX10001-009-001-001 to Z.C., 2012ZX1000-1006-001-009 to H.S.) Beijing Key Laboratory of HIV/AIDS Research (BZ0089 to H.Wu) and Beijing Municipal of Science and Technology Major Project (D161100000416003 to H.Wu) and the University Development Fund of the University of Hong Kong and Li Ka Shing Faculty of Medicine Matching Fund to AIDS Institute. Publisher Copyright: {\textcopyright} 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2017",
month = oct,
doi = "10.1038/s41564-017-0006-5",
language = "English",
volume = "2",
pages = "1389--1402",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Research",
}
