{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:05:31Z","timestamp":1791234331008,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,4]],"date-time":"2021-04-04T00:00:00Z","timestamp":1617494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK109883"],"award-info":[{"award-number":["R01DK109883"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P51OD011104"],"award-info":[{"award-number":["P51OD011104"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Transforming growth factor-\u03b2 signaling (TGF-\u03b2) maintains a balanced physiological function including cell growth, differentiation, and proliferation and regulation of immune system by modulating either SMAD2\/3 and SMAD7 (SMAD-dependent) or SMAD-independent signaling pathways under normal conditions. Increased production of TGF-\u03b2 promotes immunosuppression in Human Immunodeficiency Virus (HIV)\/Simian Immunodeficiency Virus (SIV) infection. However, the cellular source and downstream events of increased TGF-\u03b2 production that attributes to its pathological manifestations remain unknown. Here, we have shown increased production of TGF-\u03b2 in a majority of intestinal CD3\u2212CD20\u2212CD68+ cells from acute and chronically SIV infected rhesus macaques, which negatively correlated with the frequency of jejunum CD4+ T cells. No significant changes in intestinal TGF-\u03b2 receptor II expression were observed but increased production of the pSMAD2\/3 protein and SMAD3 gene expression in jejunum tissues that were accompanied by a downregulation of SMAD7 protein and gene expression. Enhanced TGF-\u03b2 production by intestinal CD3\u2212CD20\u2212CD68+ cells and increased TGF-\u03b2\/SMAD-dependent signaling might be due to a disruption of a negative feedback loop mediated by SMAD7. This suggests that SIV infection impacts the SMAD-dependent signaling pathway of TGF-\u03b2 and provides a potential framework for further study to understand the role of viral factor(s) in modulating TGF-\u03b2 production and downregulating SMAD7 expression in SIV. Regulation of mucosal TGF-\u03b2 expression by therapeutic TGF-\u03b2 blockers may help to create effective antiviral mucosal immune responses.<\/jats:p>","DOI":"10.3390\/cells10040806","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T11:48:29Z","timestamp":1617623309000},"page":"806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Enhanced Intestinal TGF-\u03b2\/SMAD-Dependent Signaling in Simian Immunodeficiency Virus Infected Rhesus Macaques"],"prefix":"10.3390","volume":"10","author":[{"given":"Nongthombam","family":"Boby","sequence":"first","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9936-0852","authenticated-orcid":false,"given":"Alyssa","family":"Ransom","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barcley T.","family":"Pace","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7640-2282","authenticated-orcid":false,"given":"Kelsey M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Mabee","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita","family":"Das","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudesh K.","family":"Srivastav","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Tulane University, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4656-5264","authenticated-orcid":false,"given":"Edith","family":"Porter","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, California State University Los Angeles, Los Angeles, CA 90032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1949-973X","authenticated-orcid":false,"given":"Bapi","family":"Pahar","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA"},{"name":"Tulane University School of Medicine, Tulane University, New Orleans, LA 70112, USA"},{"name":"Tulane School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.clim.2015.03.001","article-title":"Transforming growth factor-\u03b21 regulated phosphorylated AKT and interferon gamma expressions are associated with epithelial cell survival in rhesus macaque colon explants","volume":"158","author":"Pahar","year":"2015","journal-title":"Clin. 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