{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:24:25Z","timestamp":1790745865069,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Hospital Clinical Research Program","award":["AOM 11\u00e2\u20ac\u201c250"],"award-info":[{"award-number":["AOM 11\u00e2\u20ac\u201c250"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mesenchymal stromal cells (MSCs) have recently emerged as an interesting therapeutic approach for patients with progressive systemic sclerosis (SSc), a rare and life-threatening orphan autoimmune disease. Whereas MSC immunomodulatory potential is considered as a central mechanism for their clinical benefit, very few data are available on the impact of MSCs on immune cell subsets in vivo. In the current extended study of a phase I\/II clinical trial exploring the injection of a single dose of allogeneic bone marrow-MSCs (alloBM-MSCs) in patients with severe SSc (NCT02213705), we performed a longitudinal in-depth characterization of circulating immune cells in 19 MSC-treated patients, including 14 responders and 5 non-responders. By a combination of flow cytometry and transcriptomic analyses, we highlighted an increase in circulating CD24hiCD27posCD38lo\/neg memory B cells, the main IL-10-producing regulatory B cell (Breg) subset, and an upregulation of IL10 expression in ex-vivo purified B cells, specifically in responder patients, early after the alloBM-MSC infusion. In addition, a deeper alteration of the B-cell compartment before alloBM-MSC treatment, including a higher expression of profibrotic cytokines IL6 and TGF\u03b2 by sorted B cells was associated with a non-responder clinical status. Finally, BM-MSCs were able to directly upregulate IL-10 production in activated B cells in vitro. These data suggest that cytokine-producing B cells, in particular Breg, are pivotal effectors of BM-MSC therapeutic activity in SSc. Their quantification as activity biomarkers in MSC potency assays and patient selection criteria may be considered to reach optimal clinical benefit when designing MSC-based clinical trials.<\/jats:p>","DOI":"10.1093\/stcltm\/szad010","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T15:21:25Z","timestamp":1678980085000},"page":"194-206","source":"Crossref","is-referenced-by-count":27,"title":["Regulatory B Cells Contribute to the Clinical Response After Bone Marrow-Derived Mesenchymal Stromal Cell Infusion in Patients With Systemic Sclerosis"],"prefix":"10.1093","volume":"12","author":[{"given":"S\u00e9verine","family":"Loisel","sequence":"first","affiliation":[{"name":"SITI, CHU Rennes, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"},{"name":"INSERM UMR 1236, Universit\u00e9 Rennes, INSERM, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Lansiaux","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de M\u00e9decine Interne (UF 04), CRMR Maladies auto-immunes et th\u00e9rapie cellulaire (MATHEC), Centre de R\u00e9f\u00e9rence des Maladies auto-immunes syst\u00e9miques Rares d\u2019Ile-de-France, AP-HP , H\u00f4pital St-Louis, Paris , France"},{"name":"Universit\u00e9 de Paris Cit\u00e9, IRSL, Recherche clinique appliqu\u00e9e \u00e0 l\u2019h\u00e9matologie , URP 3518 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Rossille","sequence":"additional","affiliation":[{"name":"SITI, CHU Rennes, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"},{"name":"INSERM UMR 1236, Universit\u00e9 Rennes, INSERM, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nad\u00e8ge","family":"Bescher","sequence":"additional","affiliation":[{"name":"SITI, CHU Rennes, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"},{"name":"INSERM UMR 1236, Universit\u00e9 Rennes, INSERM, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"B\u00e9zier","sequence":"additional","affiliation":[{"name":"SITI, CHU Rennes, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"},{"name":"INSERM UMR 1236, Universit\u00e9 Rennes, INSERM, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u00eblle","family":"Latour","sequence":"additional","affiliation":[{"name":"SITI, CHU Rennes, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"},{"name":"INSERM UMR 1236, Universit\u00e9 Rennes, INSERM, 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France"},{"name":"Department of Medicine, McGill University , Montreal , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-917X","authenticated-orcid":false,"given":"Karin","family":"Tarte","sequence":"additional","affiliation":[{"name":"SITI, CHU Rennes, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"},{"name":"INSERM UMR 1236, Universit\u00e9 Rennes, INSERM, Etablissement Fran\u00e7ais du Sang Bretagne , Rennes , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"issue":"10103","key":"2023041713255246600_","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","article-title":"Systemic 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