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

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.