Andrew Taylor
Research Story
A large part of our research effort has been to characterize the immunosuppressive and immunoregulating factors within immune privilege tissues. Through immunochemical and biological analysis of aqueous humor, the fluid filling the anterior chamber of the eye, we have identified several potent immunoregulating and immunosuppressing neuropeptides that 1) suppress the activation of effector Th1 cells, 2) suppress the activation and the inflammatory activity of macrophages, and 3) mediate the induction of antigen-specific regulatory T cells.
Our research has found constitutively present neuropeptides in the immune privileged eye, such as alpha-melanocyte stimulating hormone (a-MSH), vasoactive intestinal peptide, calcitonin gene related peptide, and somatostatin. Collectively, the neuropeptides in aqueous humor suppress activation of delayed type hypersensitivity of adaptive immunity, and endotoxin activation of macrophages in innate immunity. Individually, the neuropeptides target different cells, and stages in the induction of an immune response. The result is that a mechanism of ocular immune privilege is to manipulate immunity to regulate, and suppress itself.
We are finding that within the ocular microenvironment the activation of macrophages by pathogens does not promote inflammation, but promotes suppressor functionality in the macrophages. These macrophages respond without mediating inflammation, or activating T cells. Moreover, the macrophages produce anti-inflammatory cytokines, suppress, and possibly induce apoptosis in activated T cells. They also produce enzymes associated with wound repair. We are finding that this is mediated by neuropeptides produced and released by healthy retinal pigment epithelial
As we continue to examine the mechanisms of ocular immune privilege we further promote the importance of the interactions between the nervous and the immune systems and how we can use these interactions to beneficially manipulate immunity to prevent hypersensitivity, transplantation graft rejection, and autoimmune diseases.
