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Abnormal proliferation, apoptosis, and differentiation of CD4<jats:sup>+<\/jats:sup> T cells are key factors in the pathogenesis of pSS. Autophagy is one of the important mechanisms to maintain immune homeostasis and function of CD4<jats:sup>+<\/jats:sup> T cells. Human umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) may simulate the immunoregulation of MSCs while avoiding the risks of MSCs treatment. However, whether UCMSC-Exos can regulate the functions of CD4<jats:sup>+<\/jats:sup> T cells in pSS, and whether the effects via the autophagy pathway remains unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The study analyzed retrospectively the peripheral blood lymphocyte subsets in pSS patients, and explored the relationship between lymphocyte subsets and disease activity. Next, peripheral blood CD4<jats:sup>+<\/jats:sup> T cells were sorted using immunomagnetic beads. The proliferation, apoptosis, differentiation, and inflammatory factors of CD4<jats:sup>+<\/jats:sup> T cells were determined using flow cytometry. Autophagosomes of CD4<jats:sup>+<\/jats:sup> T cells were detected using transmission electron microscopy, autophagy-related proteins and genes were detected using western blotting or RT-qPCR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The study demonstrated that the peripheral blood CD4<jats:sup>+<\/jats:sup> T cells decreased in pSS patients, and negatively correlated with disease activity. UCMSC-Exos inhibited excessive proliferation and apoptosis of CD4<jats:sup>+<\/jats:sup> T cells in pSS patients, blocked them in the G0\/G1 phase, inhibited them from entering the S phase, reduced the Th17 cell ratio, elevated the Treg ratio, inhibited IFN-\u03b3, TNF-\u03b1, IL-6, IL-17A, and IL-17F secretion, and promoted IL-10 and TGF-\u03b2 secretion. UCMSC-Exos reduced the elevated autophagy levels in the peripheral blood CD4<jats:sup>+<\/jats:sup> T cells of patients with pSS. Furthermore, UCMSC-Exos regulated CD4<jats:sup>+<\/jats:sup> T cell proliferation and early apoptosis, inhibited Th17 cell differentiation, promoted Treg cell differentiation, and restored the Th17\/Treg balance in pSS patients through the autophagy pathway.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The study indicated that UCMSC-Exos exerts an immunomodulatory effect on the CD4<jats:sup>+<\/jats:sup> T cells, and maybe as a new treatment for pSS.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10787-023-01189-x","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T18:02:50Z","timestamp":1680544970000},"page":"1823-1838","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Immunomodulatory effects of umbilical mesenchymal stem cell-derived exosomes on CD4+ T cells in patients with primary Sj\u00f6gren's syndrome"],"prefix":"10.1007","volume":"31","author":[{"given":"Dan","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zewen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoqi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-4872","authenticated-orcid":false,"given":"Liyun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"issue":"1","key":"1189_CR1","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s13075-017-1385-y","volume":"19","author":"C Alessandri","year":"2017","unstructured":"Alessandri C, Ciccia F, Priori R, Astorri E, Guggino G, Alessandro R et al (2017) CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sj\u00f6gren\u2019s syndrome patients and correlates with focus score and disease activity. 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