Immune Modulatory Effects of Mesenchymal Stem Cells Mediated by Lymphocyte Recruitment

Immunomodulators, including recombinant proteins, immunoglobulins, and cell therapeutics, can activate or suppress the human immune system. Mesenchymal stem cells have immunoregulatory functions and could be used as cell therapeutics. In this study, we hypothesized that exogenous MSCs would regulate the immune response by influencing the recruitment of T lymphocytes in peripheral tissues. In a mouse allogeneic bone marrow transplantation model, bone marrow with MSCs from C57BL/6 mice (H-2^b) was transferred to BALB/c mice (H-2^d) pre-conditioned with busulfan-cyclophosphamide. The proportion of CD3⁺ cells in the spleen was lower in the MSC co-transplantation group. When MSCs were administered, the expression of CD69 decreased in the spleen, while CD62L increased in the blood. In vitro, T-MSC co-cultured splenic T cells showed decreased expression of CCRL2, ACKR2, IFNG, TLR4, CXCR2, CCL5, CCR5, IL4, and CCL20 and increased expression of CXCL9, ACTB, CXCR6, CCR9, CCR4, CCL28, and MAPK1. This study provides a clue to the immune modulatory effect of MSCs by regulating lymphocyte migration in the peripheral lymphoid tissues by secreting chemokines, inducing chemokine receptor expression, or CD69-mediated regulation.