Actions of Retinoic Acid in the Pathophysiology of HIV Infection

• Type of Material: Article
• Authors: Neil Sidell, Emory University; Maureen A Kane, University of Maryland
• Language: English
• Date: 2022-04-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/nu14081611
• Title of Journal or Parent Work: NUTRIENTS
• Volume: 14
• Issue: 8
• Grant/Funding Information: This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. HHSN272201000046C and HHSN272201500013I; National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development grant no. R01HD077260. Additional support was provided by the University of Maryland School of Pharmacy Mass Spectrometry Center (SOP1841-IQB2014). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the funders.
• Keywords: mucosal immunity; retinoids; Life Sciences & Biomedicine; NONHUMAN PRIMATE MODEL; NATURAL-KILLER-CELLS; HIV; Science & Technology; EXPRESSION; immune regulation; TRANSCRIPTION FACTOR GATA3; INNATE LYMPHOID-CELLS; INTEGRIN ALPHA(4)BETA(7); REGULATORY T-CELLS; VITAMIN-A; RHESUS MACAQUES; retinoic acid; Nutrition & Dietetics; INTESTINAL DENDRITIC CELLS
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, Pharmacy

Abstract

The vitamin A metabolite all-trans retinoic acid (RA) plays a key role in tissue homeostasis and mucosal immunity. RA is produced by gut-associated dendritic cells, which are among the first cells encountered by HIV. Acute HIV infection results in rapid reduction of RA levels and dysregulation of immune cell populations whose identities and function are largely controlled by RA. Here, we discuss the potential link between the roles played by RA in shaping intestinal immune responses and the manifestations and pathogenesis of HIV-associated enteropathy and similar conditions observed in SIV-infected non-human primate models. We also present data demonstrating the ability of RA to enhance the activation of replication-competent viral reservoirs from subjects on suppressive anti-retroviral therapy. The data suggest that retinoid supplementation may be a useful adjuvant for countering the pathologic condition of the gastro-intestinal tract associated with HIV infection and as part of a strategy for reactivating viral reservoirs as a means of depleting latent viral infection.