MAdCAM-1 costimulation in the presence of retinoic acid and TGF-β promotes HIV infection and differentiation of CD4+ T cells into CCR5+ TRM -like cells.
Sinmanus VimonpatranonLivia R GoesAmanda ChanIsabella LicavoliJordan McMurrySamuel R WertzAnush ArakelyanDawei HuangAndrew JiangCindy HuangJoyce ZhouJason YolitzAlexandre GirardDonald Van RykDanlan WeiIl Young HwangCraig MartensKishore KanakabandiKimmo VirtanevaStacy RicklefsBenjamin P DarwitzMarcelo A SoaresKovit PattanapanyasatAnthony S FauciJames ArthosClaudia CicalaPublished in: PLoS pathogens (2023)
CD4+ tissue resident memory T cells (TRMs) are implicated in the formation of persistent HIV reservoirs that are established during the very early stages of infection. The tissue-specific factors that direct T cells to establish tissue residency are not well defined, nor are the factors that establish viral latency. We report that costimulation via MAdCAM-1 and retinoic acid (RA), two constituents of gut tissues, together with TGF-β, promote the differentiation of CD4+ T cells into a distinct subset α4β7+CD69+CD103+ TRM -like cells. Among the costimulatory ligands we evaluated, MAdCAM-1 was unique in its capacity to upregulate both CCR5 and CCR9. MAdCAM-1 costimulation rendered cells susceptible to HIV infection. Differentiation of TRM -like cells was reduced by MAdCAM-1 antagonists developed to treat inflammatory bowel diseases. These finding provide a framework to better understand the contribution of CD4+ TRMs to persistent viral reservoirs and HIV pathogenesis.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- hiv aids
- hiv testing
- dendritic cells
- sars cov
- regulatory t cells
- hepatitis c virus
- transforming growth factor
- men who have sex with men
- rheumatoid arthritis
- gene expression
- patient safety
- working memory
- south africa
- oxidative stress
- cell proliferation
- interstitial lung disease
- idiopathic pulmonary fibrosis