Self Recognition and Autoimmunity

Certain tissues in the body including the eye are relatively resistant to autoimmune injury and are referred to as immune privileged sites.  Andrew Taylor studies the factors that contribute to immune privilege and he has identified a number of neuropeptides in the fluid filling the anterior chamber of the eye that have potent immunosuppressive and immunoregulatory effects on T cells and macrophages.  Understanding the mechanisms responsible for immune privilege may enable these pathways to be manipulated to regulate diverse inflammatory disorders.

Gustavo Mostoslavsky is interested in stem cells and their potential clinical applications in two broad areas.  He has developed a novel method to generate induced Pluripotent Stem cells (iPS cells) and is using iPS cells as well as embryonic stem cells to study how intestinal lineage cells develop and whether iPS cells may have potential for regenerative medicine with respect to intestinal tissue.  He is also investigating whether hematopoietic stem cell manipulation using lentiviral vectors expressing particular genes of interest might be an effective approach for the correction of various immunodeficiency disorders.

Gregory Viglianti’s focus is on defining the protein and nucleic acid composition of the ribonucleoprotein and chromatin related autoantigens characteristic of the autoimmune disease systemic lupus erythematosus and determining which specific forms of cell death lead to their release.  These autoantigens are directly immunostimulatory and are thought to contribute to lupus pathogenesis through their ability to activate specific receptors of the innate immune system, in particular Toll-like receptors (TLR) 7 and TLR9.

Robert Lafyatis studies the autoimmune disease systemic sclerosis (scleroderma) using both animal models and patient-derived clinical material.  He is investigating how endogenous and exogenous innate immune stimuli regulate fibrosis and vascular injury, two central disease manifestations of systemic sclerosis.  Intriguingly, as in lupus, TLRs appear to be important in mediating these effects and this has led to collaborations between Dr. Lafyatis and investigators at BU who study lupus.

Ian Rifkin has two main areas of interest related to systemic lupus erythematosus.  The first is the role of TLRs in mediating disease pathogenesis through engagement of nucleic acid-containing autoantigens in dendritic cells.  More recently he has focused on how interferon regulatory factor 5, a TLR signaling molecule, contributes both to dendritic cell activation and disease development more generally.  The second area of interest relates to the factors that lead to premature atherosclerosis in patients with lupus and how modulation of inflammatory pathways can reduce the development of atherosclerosis in lupus.

Faculty involved in this research are: