Kohtaro Fujihashi
Research Interests of Kohtaro Fujihashi
The mucosal immune system is an internet of tissues, cells and biologic mediators which regulate host responses to the environment. Over 80 % of this immune system occurs in the gastrointestinal (GI) tract and the three major manifestations, e.g., mucosal immunity, inflammation and tolerance can be most conveniently studied there. For example, immunoglobulin A (IgA) is the major antibody isotype found in higher mammals, and represents 70 - 90 % or > 95 % of humoral mucosal immunity in the GI tract of humans and mice, respectively.
How do higher mammals regulate this distinct isotype pattern and allow predominant secretory IgA (S-IgA) responses at mucosal sites?
It is now clear that infection, allergies as well as immune diseases can result in significant mucosal inflammation. Specific examples include induction of CD4+ Th2 cells secreting IL-4 with regulation of mucosal IgE synthesis and mast cell-mediated, type I hypersensitivity. Recently developed murine models of inflammatory bowel disease (IBD), e.g, TCRα, or IL-2 or IL-10 knockout mice spontaneously develop either colonic inflammation or more generalized intestinal inflammatory disease.
Further, various types of human Periodontal Diseases (PD) are caused by certain anaerobic bacteria, and the specific gingival cell types are similar to those which occur in IBD.
What are the regulatory cells and cytokines responsible for development of mucosal IBD and PD ?
It is noteworthy that ingestion (or inhalation) of soluble proteins, peptides and haptens most often leads to a state of systemic unresponsiveness to parenteral immunization with these molecules, and this condition is now termed mucosally-induced tolerance. The results which are emerging are that the manner in which antigens are encountered by the mucosal immune system can determine the outcome, e.g., mucosal and systemic T cell and antibody responses versus tolerance.
What is the role of antigen presentation for induction of regulatory cells and cytokines which determine whether mucosal immunity or tolerance will develop ?
The broad research interests discussed above have significant clinical applications which range from development of mucosal vaccines, to studies of mucosal allergies, inflammation or the development of tolerance to self antigens to prevent autoimmune diseases. A number of research projects are underway in our group and these NIH-funded studies involve a number of significant collaborations both at UAB as well as with other Universities and Research Institutes. Specifically, individual projects include
- The Cellular and Molecular Mechanisms for Mucosal Immunity in the elderly;
- A Mucosal Internet of γδ, αβ T Cells and Epithelial Cells for innate and adoptive Mucosal Immunity (including salivary IgA responses);
- Molecular and Cellular Mechanisms for Induction and Regulation of Mucosal Tolerance. ;
- Mucosal Immunity in Murine Models of IBD ;
- Molecular Pathogenesis / Immunity in Periodontal Disease.