Yang-Xin Fu, MD, PhD

Professor

Contact

Department of Pathology and Immunology
The University of Chicago
5841 S. Maryland AMB S-354, MC3083
Chicago, IL 60637
Phone: (773) 702-0929
Fax: (773) 834-8940
yfu@midway.uchicago.edu

Research Interests

We are interested in defining the essential components of the lymphoid microenviron-
ment required for the development and function of the immune system.  Using a comprehensive system of knockout mice and receptor fusion proteins, we have found that lymphotoxin (LT) and TNF are essential for immune cell migrations and formation of lymphoid structures.  In addition, our recent work indicates that ligands for LT receptor are essential for the generation and migration of autoreactive T cells.  We are currently extending our research areas into other LT/TNF family members.

The next phase of my research plan will focus upon the following aims:

1. The role of LT, LIGHT, and TNF in the development of microenvironment for systemic immune responses.  LT-deficient mice have impaired total IgA, IgE, and altered anti-specific IgG responses.  We are dissecting various mechanisms by which LT control various Ig production.  We are generating transgenic mice that express LT, LIGHT, and TNF on T, B, and dendritic cells.  By breeding back to LT, LIGHT, and TNF knockout mice, mice expressing these TNF family ligands only on a specific lineage will be available.  The role of subset of LT-producing cells will be further explored.  We will further define the role of these LT-expressing cells in the development and function of non-T and non-B cells, including FDC, DC and NK cells.  In addition, the role of these cells in various autoimmune diseases will be explored, including experimental autoimmune encephalitis (EAE), autoimmune diabetes, and lupus.  Using combination of transgenic and KO mice, we will study the signal pathway of core LT family members.

2. The modulation of immune response by newly discovered TNF family members.  We have recently cloned and expressed the several TNF family members that may promote or inhibit autoimmune diseases.  Using transgenic mice and receptor fusion proteins, we have found that some of members play important role in both central and peripheral tolerance.  We are now developing and using various autoimmune diabetes, lupus, and  EAE model to study the role of these TNF members in induction and maintenance of autoimmunity.  Our recent study indicates that naïve and activated CD4 and CD8+ cells may differentially respond to TNF family ligands.  We are studying the mechanisms behind the observation.

3. The role of lymphoid tissues in the immune responses.  We can readily generate various congenital lymphoid tissue deficient mice, which can be used as a model to study the role of such lymphoid tissues in immune responses. 

4. The role of agonistic antibodies and TNF superfamily receptor fusion proteins in the development of immunity and autoimmunity.  Unexpectedly, we have found that an agonistic antibody to 4-1BB, a TNF family member, can block the development of autoimmune diseases.  We are investigating the signaling pathways and cell type involved in the inhibition.  Receptor fusion protein can be used to study the role functions of various ligands in the different stages of immune response.