title: Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjögren syndrome.
abstract: Sjögren syndrome (SS) is a systemic autoimmune disease characterized by dry mouth and eyes, and the cellular and molecular mechanisms for its pathogenesis are complex. Here we reveal, for the first time, that bone marrow mesenchymal stem cells in SS-like NOD/Ltj mice and human patients were defective in immunoregulatory functions. Importantly, treatment with mesenchymal stem cells (MSCs) suppressed autoimmunity and restored salivary gland secretory function in both mouse models and SS patients. MSC treatment directed T cells toward Treg and Th2, while suppressing Th17 and Tfh responses, and alleviated disease symptoms. Infused MSCs migrated toward the inflammatory regions in a stromal cell-derived factor-1-dependent manner, as neutralization of stromal cell-derived factor-1 ligand CXCR4 abolished the effectiveness of bone marrow mesenchymal stem cell treatment. Collectively, our study suggests that immunologic regulatory functions of MSCs play an important role in SS pathogenesis, and allogeneic MSC treatment may provide a novel, effective, and safe therapy for patients with SS.
authors.affiliation: Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
authors.forename: Junji
authors.initials: J
authors.lastname: Xu
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.forename: Dayong
authors.initials: D
authors.lastname: Liu
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Fan
authors.forename: Huayong
authors.initials: H
authors.lastname: Zhang
authors.forename: Ousheng
authors.initials: O
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Ding
authors.forename: Runtao
authors.initials: R
authors.lastname: Gao
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Ding
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Bromberg
authors.forename: Wanjun
authors.initials: W
authors.lastname: Chen
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000166:cytology / Q000276:immunology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D054377:Chemokine CXCL12; D012333:RNA, Messenger; D019718:Receptors, CXCR4