title: Mesenchymal stem cells regulate the proliferation of T cells via the growth-related oncogene/CXC chemokine receptor, CXCR2.
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.
authors.affiliation: Graduate School of Life Science and Biotechnology, CHA University, Seoul 135-081, Republic of Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Won
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Park
authors.forename: Hyeon-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
authors.forename: Dong-Ku
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000276:immunology / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D036101:Cord Blood Stem Cell Transplantation; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D053614:Janus Kinase 2 / Q000276:immunology / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D023063:Receptors, Interleukin-8B / Q000276:immunology* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C499707:CXCL3 protein, human; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D023063:Receptors, Interleukin-8B; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2