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New Th17-specific therapeutic strategies for HIV remission

Planas, Delphinea,b; Routy, Jean-Pierrec,d; Ancuta, Petronelaa,b

Current Opinion in HIV and AIDS: March 2019 - Volume 14 - Issue 2 - p 85–92
doi: 10.1097/COH.0000000000000522
T-CELLS IN HIV INFECTION: Edited by Mathias Lichterfeld and Tony Kelleher

Purpose of review This review highlights current knowledge on the dichotomous role played by T helper 17 cells (Th17)-polarized CD4+ T cells in maintaining mucosal immunity homeostasis versus fueling HIV/simian immunodeficiency virus (SIV) replication/persistence during antiretroviral therapy (ART), with a focus on molecular mechanisms underlying these processes.

Recent finding Th17 cells bridge innate and adaptive immunity against pathogens at mucosal barrier surfaces. Th17 cells are located at portal sites of HIV/SIV entry, express a unique transcriptional/metabolic status compatible with viral replication, and represent the first targets of infection. The paucity of Th17 cells during HIV/SIV infection is caused by infection itself, but also by an altered Th17 differentiation, survival, and trafficking into mucosal sites. This causes major alterations of mucosal barrier integrity, microbial translocation, and disease progression. Unless initiated during the early acute infection phases, ART fails to restore the frequency/functionality of mucosal Th17 cells. A fraction of Th17 cells is long-lived and carry HIV reservoir during ART. Recent studies identified Th17-specific host factors controlling HIV transcription, a step untargeted by current ART.

Summary The identification of molecular mechanisms contributing to HIV replication/persistence in mucosal Th17 cells paves the way toward the design of new Th17-specific therapeutic strategies aimed at improving mucosal immunity in HIV-infected individuals.

aCHUM Research Centre

bFaculty of Medicine, Département de microbiologie, infectiologie et immunologie, Université de Montréal

cChronic Viral Illness Service and Research Institute

dDivision of Hematology, McGill University Health Centre, Montreal, Quebec, Canada

Correspondence to Petronela Ancuta, CHUM Research Centre, 900 rue Saint-Denis, Tour Viger R, Room R09.416, Montreal, Quebec H2X 0A9, Canada. Tel: +514-890-8000, Ext #35744; fax: +514 412-7936; e-mail:

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