Mesenchymal stem cells regulate the proliferation of T cells via the growth-related oncogene/CXC chemokine receptor, CXCR2

Yong-Soo Lee; Kyung-Jong Won; Sung-Won Park; Hyeon-Woo Lee; Bokyung Kim; Jin-Hoi Kim; Dong-Ku Kim

doi:10.1016/j.cellimm.2012.08.002

Mesenchymal stem cells regulate the proliferation of T cells via the growth-related oncogene/CXC chemokine receptor, CXCR2

Cell Immunol. 2012 Sep;279(1):1-11. doi: 10.1016/j.cellimm.2012.08.002. Epub 2012 Sep 5.

Authors

Yong-Soo Lee¹, Kyung-Jong Won, Sung-Won Park, Hyeon-Woo Lee, Bokyung Kim, Jin-Hoi Kim, Dong-Ku Kim

Affiliation

¹ Graduate School of Life Science and Biotechnology, CHA University, Seoul 135-081, Republic of Korea.

PMID: 23023221
DOI: 10.1016/j.cellimm.2012.08.002

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Apoptosis / drug effects
Apoptosis / immunology
Cell Proliferation*
Cells, Cultured
Chemokine CXCL1 / immunology
Chemokine CXCL1 / metabolism
Chemokine CXCL2 / immunology
Chemokine CXCL2 / metabolism
Chemokines, CXC / immunology
Chemokines, CXC / metabolism
Chemokines, CXC / pharmacology
Cord Blood Stem Cell Transplantation
Flow Cytometry
HeLa Cells
Humans
Janus Kinase 2 / immunology
Janus Kinase 2 / metabolism
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells / immunology*
Mesenchymal Stem Cells / metabolism
Mice
Mice, Inbred NOD
Mice, SCID
Microscopy, Fluorescence
Phosphorylation
Receptors, Interleukin-8B / immunology*
Receptors, Interleukin-8B / metabolism
STAT3 Transcription Factor / immunology
STAT3 Transcription Factor / metabolism
T-Lymphocytes / drug effects
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
Xenograft Model Antitumor Assays / methods

Substances

CXCL3 protein, human
Chemokine CXCL1
Chemokine CXCL2
Chemokines, CXC
Receptors, Interleukin-8B
STAT3 Transcription Factor
Janus Kinase 2