Nancy Hartman Ruddle PhD
Professor Emeritus of and Senior Research Scientist in Epidemiology (Microbial Diseases)
Cell trafficking and inflammation in autoimmunity and lymphoid organ development
We study cell trafficking and inflammation in autoimmunity and lymphoid organ development, particularly the roles of members of the lymphotoxin/tumor necrosis factor (LT/??TNF) family. We study acute inflammation and animal models of autoimmune diseases, including Type 1 diabetes mellitus and multiple sclerosis. LT is also crucial for lymphoid organ development; LT deficient mice lack lymph nodes and Peyer’s patches and exhibit profound alterations in spleen and nasal associated lymphoid tissue. Our studies demonstrate that cytokines’ functions in lymphoid organ development and inflammation are similar; they regulate chemokines and vascular adhesion molecules. Ectopic or “tertiary” lymphoid organs arising in chronic inflammation are lymphoid accumulations that permit the presentation of foreign and self-antigens at local sites of inflammation. Our studies on high endothelial venules and lymphatic vessels elucidate developmental mechanisms and point the way towards treatment and prevention of chronic inflammation.
Extensive Research Description
Professor Ruddle's research concentrates on cell trafficking and inflammation, particularly with regard to the lymphotoxin/tumor necrosis factor (LT/TNF) family. Her group studies these and other cytokines in autoimmune and infectious diseases. They study autoimmune diseases, the inflammatory stage of Type 1 diabetes mellitus, and experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Cytokines, autoantigens, or infectious organisms can give rise to chronic cellular accumulations called "ectopic" or "tertiary lymphoid organs," through a process termed lymphoid organ neogenesis. Three “tertiary lymphoid organs” can contribute to diseases and even serve as a site of prion accumulations. Dr. Ruddle’s group identified a role for LT in normal lymphoid organ development. Their studies demonstrate that the roles of the cytokines in lymphoid organ development and inflammation are similar, in that in both contexts they induce chemokines and vascular adhesion molecules. The functions of lymph nodes and tertiary lymphoid organs may be comparable with regard to antigen presentation, serving both helpful and harmful roles in defense and autoimmunity.