{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:50:00Z","timestamp":1782978600845,"version":"3.54.5"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>A well-balanced maternal immune system is crucial to maintain fetal tolerance in case of infections during pregnancy. Immune adaptations include an increased secretion of soluble mediators to protect the semi-allogeneic fetus from excessive pro-inflammatory response. B lymphocytes acquire a higher capacity to express CD83 and secrete soluble CD83 (sCD83) upon exposure to bacteria-derived components such as LPS. CD83 possesses immune modulatory functions and shows a promising therapeutic potential against inflammatory conditions. The administration of sCD83 to pregnant mice reduces LPS-induced abortion rates. The increased CD83 expression by endometrial B cells as compared to peripheral blood B cells suggests its modulatory role in the fetal tolerance, especially in the context of infection. We postulate that in pregnancy, CD83 expression and release is controlled by pregnancy-related hormones. The intra- and extracellular expression of CD83 in leukocytes from peripheral blood or <jats:italic>decidua basalis<\/jats:italic> and <jats:italic>parietalis<\/jats:italic> at term were analyzed by flow cytometry. After treatment with pregnancy-related hormones and LPS, ELISA and qPCR were performed to study sCD83 release and <jats:italic>CD83<\/jats:italic> gene expression, respectively. Cleavage prediction analysis was used to find potential proteases targeting CD83. Expression of selected proteases was analyzed by ELISA. Higher levels of CD83 were found in CD11c<jats:sup>+<\/jats:sup> dendritic cells, CD3<jats:sup>+<\/jats:sup> T cells and CD19<jats:sup>+<\/jats:sup> B cells from <jats:italic>decidua basalis<\/jats:italic> and <jats:italic>decidua parietalis<\/jats:italic> after LPS-stimulation <jats:italic>in vitro<\/jats:italic>. An increase of intracellular expression of CD83 was also detected in CD19<jats:sup>+<\/jats:sup> B cells from both compartments. Stimulated B cells displayed significantly higher percentages of CD83<jats:sup>+<\/jats:sup> cells than dendritic cells and T cells from <jats:italic>decidua basalis<\/jats:italic> and peripheral blood. Treatment of B lymphocytes with pregnancy-related molecules (E2, P4, TGF-\u03b21 and hCG) enhanced the LPS-mediated increase of CD83 expression, while dexamethasone led to a reduction. Similarly, the release of sCD83 was increased under TGF-\u03b21 treatment but decreased upon dexamethasone stimulation. Finally, we found that the hormonal regulation of CD83 expression is likely a result from a balance between gene transcription from <jats:italic>CD83<\/jats:italic> and the modulation of the metalloproteinase MMP-7. Thus, data supports and complements our previous murine studies on hormonal regulation of CD83 expression, reinforcing its immunomodulatory relevance in anti-bacterial responses during pregnancy.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1452879","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T04:31:21Z","timestamp":1726115481000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Pregnancy-related factors induce immune tolerance through regulation of sCD83 release"],"prefix":"10.3389","volume":"15","author":[{"given":"Pauline","family":"Krupa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Wein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea 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