دورية أكاديمية
Regulatory B Cells Contribute to the Clinical Response After Bone Marrow-Derived Mesenchymal Stromal Cell Infusion in Patients With Systemic Sclerosis
| العنوان: | Regulatory B Cells Contribute to the Clinical Response After Bone Marrow-Derived Mesenchymal Stromal Cell Infusion in Patients With Systemic Sclerosis |
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| المؤلفون: | Loisel, Séverine, Lansiaux, Pauline, Rossille, Delphine, Ménard, Cédric, Dulong, Joëlle, Monvoisin, Céline, Bescher, Nadège, Bezier, Isabelle, Latour, Maelle, Cras, Audrey, Farge, Dominique, Tarte, Karin |
| المساهمون: | Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou, Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang Rennes (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis AP-HP (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Recherche clinique appliquée à l'hématologie (URP_3518), McGill University = Université McGill Montréal, Canada, AOM 11–250, National Hospital Clinical Research Program |
| المصدر: | ISSN: 2157-6564. |
| بيانات النشر: | HAL CCSD Wiley |
| سنة النشر: | 2023 |
| المجموعة: | Université de Rennes 1: Publications scientifiques (HAL) |
| مصطلحات موضوعية: | Breg, mesenchymal stromal cells, immune monitoring, systemic sclerosis, clinical trial, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; 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 TGFβ 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36928395; hal-04059311; https://hal.science/hal-04059311Test; https://hal.science/hal-04059311/documentTest; https://hal.science/hal-04059311/file/szad010.pdfTest; PUBMED: 36928395 |
| DOI: | 10.1093/stcltm/szad010 |
| الإتاحة: | https://doi.org/10.1093/stcltm/szad010Test https://hal.science/hal-04059311Test https://hal.science/hal-04059311/documentTest https://hal.science/hal-04059311/file/szad010.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-ncTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.91ADEFF2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/stcltm/szad010 |
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