Vimonpatranon S.Goes L.R.Chan A.Licavoli I.McMurry J.Wertz S.R.Arakelyan A.Huang D.Jiang A.Huang C.Zhou J.Yolitz J.Girard A.Van Ryk D.Wei D.Hwang I.Y.Martens C.Kanakabandi K.Virtaneva K.Ricklefs S.Darwitz B.P.Soares M.A.Pattanapanyasat K.Fauci A.S.Arthos J.Cicala C.Mahidol University2023-05-192023-05-192023-03-01PLoS Pathogens Vol.19 No.3 (2023)15537366https://repository.li.mahidol.ac.th/handle/20.500.14594/81632CD4+ 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.Biochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1371/journal.ppat.10112092-s2.0-851510439231553737436897929