Research

Immunological mechanisms in autoimmunity, allergy and heart disease

Autoimmune and allergic diseases are associated with significant morbidity and mortality and recently, their incidence has been substantially increased in Western societies. Type-1 (Th1) immune responses are necessary for protection against infectious agents and when excessive can lead to autoimmunity. Type-2 (Th2) responses are associated with defense against parasites, while aberrant Th2 cell activation may lead to allergies and asthma. Moreover, inflammation has been increasingly recognized as a critical pathologic component of heart disease. In addition, certain pathologic immunological conditions such as autoimmune diseases are also considered as important predisposing factors for cardiovascular disease. Studies from our group have shown that cytokines play a critical role in the induction of Th1-mediated autoimmune and Th2-induced allergic responses. Our goal is to further characterize the roles of two cytokines, Eta-1/Opn and Activin-A, in Th cell-mediated immunity as well as in the initiation and perpetuation of autoimmune, allergic and heart diseases.

Investigation of the role of Eta-1/Osteopontin in the development of T cell mediated immune responses
Eta-1/Osteopontin (Eta-1/Opn) is a pleiotropic cytokine considered to be involved in the differentiation of Th1/Th2 immune responses. Studies from our group have shown that Eta-1/Opn represents an essential step for the induction of Th1 immunity as it induces IL-12 and suppresses IL-10 production by macrophages in vitro. In addition, Eta-1/Opn-/- mice have reduced Th1 immune responses (DTH), sensitivity to certain infections and do not develop organ-specific autoimmunity. In humans, increased Eta-1/Opn expression has been demonstrated in synovial tissue of rheumatoid arthritis patients, in intestinal biopsies from patients with Crohn's disease and in active plaques of multiple sclerosis patients suggesting a role in Th1 immune responses and autoimmunity. However, the role of Eta-1/Opn in Th2-driven allergic diseases remains unclear.


Recent studies from our group show that Eta-1/Opn plays an important role during the induction phase of Type-2 allergic immune responses through regulation of DC subpopulations. Therefore, Eta-1/Opn represents an important molecular link between: a) antigen recognition/presentation by dendritic cells for the activation of T lymphocytes, b) T cell differentiation and immune regulation.


The main research interests of our group are: 1) to understand how Eta-1/Opn influences early events required for Th1 and Th2 differentiation and 2) to understand how Eta-1/Opn regulates chronic Th1 and Th2 inflammatory responses.