The primary role of the immune system is to protect tissues from damage by danger signals. However, sustained immune responses and uncontrolled immune cells, such as macrophages, dendritic cells, and T cells, result in inflammation and autoimmunity. Our research interest is to study the regulation of immune cell recruitment and function in the pathogenesis of inflammatory diseases such as atherosclerosis and autoimmune arthritis. The ultimate goal of our research is to make contributions to the in-depth understanding of disease mechanisms and the discoveries of new therapies in the treatment of these diseases.
Chemokine and chemokine receptors are key regulators of leukocyte trafficking. Monocytes are precursors of dendritic cells and macrophages and can be divided into two major subsets based on their distinctive expression of chemokine receptors CX3CR1 and CCR2. We and others have shown that animals that are deficient in either receptor are less susceptible to vascular injury and atherosclerosis. We have also demonstrated that the alteration of vascular dendritic cells is CX3CR1-dependent and atherosclerosis-correlated. Further investigation of mechanisms by which CX3CR1 and CCR2 regulate the recruitment and function of dendritic cells and tissue macrophages in response to vascular inflammation is one of our ongoing projects.
Th17 cells are newly identified CD4+ T helper effectors that are specifically responsible for autoimmunity and inflammation. We have recently discovered that Th17 cells and Th17 cell-mediated responses contribute to CCR2-mediated exacerbation of autoimmune arthritis. We are now investigating mechanisms underlying this phenomenon.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that suppress T cell activities and play an important role in cancer and autoimmunity. Our recent data suggest that a subset of monocytes may act as MDSCs in autoimmune arthritis. We are currently studying their cellular mechanisms of action on T cells and B cells. Their therapeutic potential is also being tested in different models of autoimmune arthritis.