Abstract
Mesenchymal stem cells (MSCs) have known to induce immunosuppressive properties by preventing T cell proliferation. However, it is remains unclear how MSCs inhibit T cell proliferation. To identify the factor that inhibits T cell proliferation, we conducted a cytokine array analysis of culture medium from a co-culture of MSCs and T cells and found that the chemokines, CXCL1, 2 and 3, were induced in T cells. MSCs also induced the expression of the CXCR2 receptor on T cell surface. Particularly, CXCL3 inhibited proliferation and increased apoptosis in T cells, which were reversed by CXCR2 inhibitor treatment. Moreover, CXCL3 decreased JAK2, STAT3, and AKT phosphorylation and these responses were also abolished by CXCR2 inhibitor treatment. MSCs suppressed the proliferation of T cells into tumor tissue. Collectively, these data demonstrate that MSCs directly regulate T cell proliferation by induction of CXCL3 chemokine and its receptor, CXCR2 on the surface in T cells.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Apoptosis / drug effects
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Apoptosis / immunology
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Cell Proliferation*
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Cells, Cultured
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Chemokine CXCL1 / immunology
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Chemokine CXCL1 / metabolism
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Chemokine CXCL2 / immunology
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Chemokine CXCL2 / metabolism
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Chemokines, CXC / immunology
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Chemokines, CXC / metabolism
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Chemokines, CXC / pharmacology
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Cord Blood Stem Cell Transplantation
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Flow Cytometry
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HeLa Cells
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Humans
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Janus Kinase 2 / immunology
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Janus Kinase 2 / metabolism
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Mesenchymal Stem Cell Transplantation
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Mesenchymal Stem Cells / immunology*
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Mesenchymal Stem Cells / metabolism
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Microscopy, Fluorescence
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Phosphorylation
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Receptors, Interleukin-8B / immunology*
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Receptors, Interleukin-8B / metabolism
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STAT3 Transcription Factor / immunology
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STAT3 Transcription Factor / metabolism
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Xenograft Model Antitumor Assays / methods
Substances
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CXCL3 protein, human
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Chemokine CXCL1
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Chemokine CXCL2
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Chemokines, CXC
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Receptors, Interleukin-8B
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STAT3 Transcription Factor
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Janus Kinase 2