This proposal is part of a career development plan integrating didactics in the form of course work in immunology with direct, mentored experience in the design and conduct of scientific research. Expertise in these areas will provide the necessary components for a successful career in asthma research. The Center for Lung Research and the Department of Microbiology and Immunology at Vanderbilt University have the necessary facilities to complete the proposed research project. The mentors and faculty in this environment are well recognized, established senior investigators. The long term goal of this research is to investigate the mechanisms regulating the development and maintenance of atopic asthma and allergic diseases. T cell function is a critical determinant of immune responses as well as susceptibility to allergic diseases. Activated T cells can differentiate into effectors whose cytokine profile is limited to type 1 (IFN-gamma dominant) or type 2 (IL-4, IL-5 dominant) patterns. Type 1 T cell effectors serve to activate cell mediated immunity and inflammatory responses, while type 2 T cell effectors are involved in the humoral response and may limit or inhibit type 1 responses. The nature of an effector response can regulate emergence of disease states such as type 1 diabetes or asthma. These patterns of differential cytokine expression are controlled through transcriptional mechanism in T cell clones and primary effector cells. Experiments in specific aim 1 will investigate the mechanism by which NF-kappaB impairs type 1 T cell effector function. As part of this aim, I will investigate the role of impaired clonal expansion and quantitate cytokine defects. Experiments proposed in specific aim 2 will investigate if type 1 T cell effectors are required for the development of antigen- inducible airway hyperresponsiveness.
In specific aim 3 we will use a dual TCR model to determine if an effector T cell repertoire can be biased through a second TCR so as to alter the susceptibility to antigen- induced airway hyperresponsiveness. This program together with the support of my mentor and co-mentor will provide me with the opportunity to become a successful independent investigator and will allow me to make a significant contribution to improving our understanding of allergic disease processes.
| Asosingh, Kewal; Hanson, Jodi D; Cheng, Georgiana et al. (2010) Allergen-induced, eotaxin-rich, proangiogenic bone marrow progenitors: a blood-borne cellular envoy for lung eosinophilia. J Allergy Clin Immunol 125:918-25 |
| Asosingh, Kewal; Erzurum, Serpil C (2009) Angioplasticity in asthma. Biochem Soc Trans 37:805-10 |
| Asosingh, Kewal; Swaidani, Shadi; Aronica, Mark et al. (2007) Th1- and Th2-dependent endothelial progenitor cell recruitment and angiogenic switch in asthma. J Immunol 178:6482-94 |
| Aronica, Mark A; McCarthy, Susan; Swaidani, Shadi et al. (2004) Recall helper T cell response: T helper 1 cell-resistant allergic susceptibility without biasing uncommitted CD4 T cells. Am J Respir Crit Care Med 169:587-95 |
