Zili Zhang Lab

human bodyThe immune system is one of the most complicated networks.   Strategically located throughout our body, the primary task of our immune system is to recognize various antigens, eliminate invading harmful microbes, and suppress tumor growth.  However, immune response is a double edged sword.  Dys-regulated immunity results in diverse diseases including asthma, eosinophilic esophagitis, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), multiple sclerosis, and uveitis (eye inflammation).  Thus, studying our immune system will help us to understand the mechanisms of many diseases and to develop more effective treatment strategies.

Just as life flourishes in our planet, our immune system also evolves to adapt the ever-changing environment.  This is exemplified by the development of T-mediated adaptive immunity, which is characterized by its long-term immune memory and rapid response to antigen re-activation. It has been well recognized for 2 decades that T helper (Th) cells can differentiate to distinctive subsets on the basis of unique gene expression and function. These unique Th subpopulations undertake special immunological tasks and responsibilities.  For instance, Th1 cells enhance cellular immunity against viral and intracellular microbial infection, while Th2 cells mediate humoral response and defense against parasites.  A dysregulated Th1 response is blamed for causing many autoimmune diseases including uveitis, and a Th2 reaction is responsible for allergy.  Furthermore, recently discovered Th17 cells express signature mediators (IL-17A/F, IL-21, IL-22, and CCL20).  They are implicated in host defense against certain microorganisms and the development of many inflammatory diseases.

Operating such complicated T cell subsets and immune components requires sophisticated machinery at a molecular level.    It is well known that, in addition to T cell receptor, an array of co-stimulatory molecules provides crucial signals to the differentiation and optimization of the T cell response. We are particularly interested in OX40 (CD134) and CD40, two co-stimulatory molecules that belong to TNF superfamily.  Our recent data suggest that OX40 participates in the activation of Th17 cells.  Furthermore, stimulation of OX40 induces CCL20 expression, thereby leading to dendritic cell and T lymphocyte trafficking in the process of immune priming. Currently, we are validating these findings in an uveitis model to further understand the meaning of these data in a disease setting.  In addition, we show that CD40 plays an important role in the pathogenesis of asthma and eosinophilic esophagitis, an emerging allergy digestive disease.  Our goal is to define the role of co-stimulatory molecules and provide an insight into novel therapeutic rationales.

Fritz Kahn - human body

 As Illustrated by Fritz Kahn, human body is an intricate and efficient “Industrial Palace”.  This is certainly the case for our complex immune system and T cell activation process.