@article{88a36842c8504b21b6bfd15d5c57faa1,
title = "HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells",
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.",
author = "Yetao Wang and Lawrence Lifshitz and Kyle Gellatly and Vinton, {Carol L.} and Kathleen Busman-Sahay and Sean McCauley and Pranitha Vangala and Kyusik Kim and Alan Derr and Smita Jaiswal and Alper Kucukural and Patrick McDonel and Hunt, {Peter W.} and Thomas Greenough and Houghton, {Jean Marie} and Ma Somsouk and Estes, {Jacob D.} and Brenchley, {Jason M.} and Manuel Garber and Deeks, {Steven G.} and Jeremy Luban",
note = "Funding Information: We thank the study participants who provided blood and colon biopsy samples, as well as their caretakers, J. Daly, S. Cheeseman and M. Wessolossky of the UMMS. C. Mannarino, A. Foley, M. McManus (UMMS) and M. Krone (UCSF) provided Institutional Review Board regulatory assistance, sample preparation and record keeping. K. Luzuriaga (UMMS) supported the patient sample database and repository. A. Ratner, S. Boswell and A. Klein (Harvard Medical School) contributed technical assistance and barcoded hydrogel beads. T. Fazzio and T. Wu provided technical support and protein A-MNase for CUT&RUN. D. Artis, L. Berg, M. Colonna, J. Huh, J. Kang, R. Rutishauser and S. Swain offered invaluable advice. This research was supported by NIH grants U01HG007910 (to M.G. and J.L.), R37AI147868 (to J.L.), R01AI111809 (to J.L.), DP1DA034990 (to J.L.), R21AI119885 (to M.G.), R01DK105837 (to M.G.) and P51OD01192 (to J.D.E. at the Oregon National Primate Research Center), and the Translational Medicine Core of the University of Massachusetts Center for AIDS Research (P30 AI042845). The UCSF-based SCOPE cohort was supported by the UCSF/Gladstone Institute of Virology and Immunology CFAR (P30 AI027763) and the CFAR Network of Integrated Systems (R24 AI067039). Additional support was provided by the Delaney AIDS Research Enterprise (AI096109 and AI127966). Funding for this study was provided in part by the Division of Intramural Research/NIAID/NIH (to J.M.B.). The content of this publication does not necessarily reflect the views or policies of DHHS, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = mar,
day = "1",
doi = "10.1038/s41590-020-0593-9",
language = "English (US)",
volume = "21",
pages = "274--286",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "3",
}