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.
Trial registration:
ClinicalTrials.gov NCT00953485.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Animals
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Autoimmunity / immunology*
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Blotting, Western
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Bone Marrow Cells / immunology*
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / pathology
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Cell Differentiation
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Cell Movement / immunology
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Cell Proliferation
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Cells, Cultured
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Chemokine CXCL12 / metabolism
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Disease Models, Animal*
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Humans
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Lymphocyte Activation
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Male
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Mesenchymal Stem Cell Transplantation*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred ICR
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Mice, Inbred NOD
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Mice, Transgenic
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Middle Aged
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Receptors, CXCR4 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Salivary Glands / cytology
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Salivary Glands / immunology
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Salivary Glands / pathology
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Sjogren's Syndrome / immunology*
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Sjogren's Syndrome / pathology
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Sjogren's Syndrome / therapy*
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T-Lymphocytes / immunology*
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / pathology
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Transplantation, Homologous
Substances
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Chemokine CXCL12
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RNA, Messenger
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Receptors, CXCR4
Associated data
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ClinicalTrials.gov/NCT00953485