Faculty and Research
Yufang Shi, DVM, PhD
Mesenchymal Stem Cells and Immune Responses
Mesenchymal stem cells (MSCs), also called multipotent mesenchymal stromal cells, exist in almost all tissues and are a key cell source for tissue repair and regeneration. Under pathological conditions, such as tissue injury, these cells are mobilized towards the site of damage. Tissue damage is usually accompanied by pro-inflammatory factors, produced by both innate and adaptive immune responses, to which MSCs are known to respond. Our studies have shown that there are bidirectional interactions between MSCs and inflammatory cells, which determine the outcome of MSC-mediated tissue repair processes. Since mesenchymal stem cells actively migrate to tumors, we are studying these cells in the tumor microenvironment and their role in tumor growth and metastasis.
We have reported that mesenchymal stem cells have
a dramatic effect on lymphocyte activation and proliferation. In vivo administration of mesenchymal stem cells could prevent the rejection of allogeneic skin grafts. Such an immunosuppressive effect was not innate to mesenchymal stem cells, rather induced by cytokines produced by lymphocytes. We are investigating the cellular and molecular mechanisms that mediate such strong immunosuppressive effects by this specialized cell population. In addition, we are also developing new strategies for clinical treatment of critical diseases such liver cirrhosis and Parkinson’s disease.
Mechanisms of Apoptosis in T Helper Subsets
Investigating the molecular mechanisms that controls activation-induced cell death (AICD) in various T cell types has been one of the major focuses of our laboratory. Our recent efforts have been on elucidating the differences of the mechanisms that control AICD in Th1 and Th2 cells as well as Tc1 and Tc2 cells. We have shown that while Th1 cells die by the Fas-mediated caspase pathway, Th2 cells die through intracellular release of granzyme B. They also found that prostaglandin E2 (PGE2) specifically protected Th2 cells from AICD by downregulating granzyme B. Thus, differences in the expression of, and susceptibility to, death effectors are a built-in mechanism that controls the Th1-Th2 as well as Tc1-Tc2 balance. One example is severer antigen induced asthma in granzyme B deficient mice.