title: Mesenchymal stromal cells infusions improve refractory chronic graft versus host disease through an increase of CD5+ regulatory B cells producing interleukin 10.
abstract: Refractory chronic graft-versus-host disease (cGVHD) is a significant complication resulting from allogeneic hematopoietic stem cell transplantation (HSCT). Mesenchymal stromal cells (MSCs) have shown promise for treating refractory cGVHD, but the favorable effects of MSCs therapy in cGVHD are complex and not fully understood. In this prospective clinical study, 20 of 23 cGVHD patients had a complete response or partial response in a 12-month follow-up study. The most marked improvements in cGVHD symptoms were observed in the skin, oral mucosa and liver. Clinical improvement was accompanied by a significantly increased number of interleukin (IL)-10-producing CD5+ B cells. Importantly, CD5+ B cells from cGVHD patients showed increased IL-10 expression after MSCs treatment, which was associated with reduced inflammatory cytokine production by T cells. Mechanistically, MSCs could promote the survival and proliferation of CD5+ regulatory B cells (Bregs), and indoleamine 2, 3-dioxygenase partially participates in the MSC-mediated effects on Breg cells. Thus, CD5+ Breg cells may have an important role in the process of MSC-induced amelioration of refractory cGVHD and may provide new clues to reveal novel mechanisms of action for MSCs.
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: K
authors.initials: K
authors.lastname: Huang
authors.affiliation: Organ Transplant Center, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Guangdong Institute for Food and Drug Control, Guangdong Food and Drug Administration, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Guangdong General Hospital, Guangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Ke
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery and Pharmacology, School of the Dental Medicine, University of Pennsylvania, Pennsylvania, PA, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 1] Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China [2] Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, China [3] Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: A P
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000293:Adolescent; D000328:Adult; D060151:B-Lymphocytes, Regulatory / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: C508609:IL10 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016753:Interleukin-10