In recent decades, the prevalence of asthma in the US and other industrialized countries has increased dramatically. Chronic allergic lung disease (allergic asthma) accounts for a majority of asthma. Many studies have demonstrated that Th2 cells and Th2 cytokines including IL-4, IL-5, and IL-13 play an important role in the development of allergic lung disease and the downstream events, including inflammation, eosinophilia, mast cell accumulation/activation, and airway remodeling. However, less is known about the mechanisms that affect the development and maintenance of Th2 cells. The proliferation and differentiation of naive T cells is triggered by interactions with antigen presenting cells bearing cognate antigen. It is becoming increasing clear that the conditions surrounding this interaction influence T cell differentiation. This proposal will investigate the role that B cells have in shaping the T cell response during chronic allergic lung disease. In addition, the role of important innate molecules will be investigated for their contribution to the regulation of B cell antigen presentation. In these studies, we investigate the role of B cells in chronic allergic lung disease, with an emphasis on the role of B cells as antigen presenting cells.
These specific aims will build a foundation for investigating the role of B cells in allergic disease, but these studies will have relevance for understanding the role of B cells in the immunology of other chronic diseases.
Chronic allergic lung disease (asthma) is characterized by inappropriate activation of the immune system. B cells are a significant contributor to this and other chronic diseases. This project focuses on the role of B cells in perpetuating allergic disease, but will give insights into how B cells contribute to the balance of tolerance versus immune activation in a variety of other diseases, as well.
|Lindell, Dennis M; Morris, Susan B; White, Maria P et al. (2011) A novel inactivated intranasal respiratory syncytial virus vaccine promotes viral clearance without Th2 associated vaccine-enhanced disease. PLoS One 6:e21823|
|Cavassani, Karen A; Carson 4th, William F; Moreira, Ana Paula et al. (2010) The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth. Blood 115:4403-11|
|Kallal, Lara E; Schaller, Matthew A; Lindell, Dennis M et al. (2010) CCL20/CCR6 blockade enhances immunity to RSV by impairing recruitment of DC. Eur J Immunol 40:1042-52|
|Schaller, Matthew A; Logue, Hannah; Mukherjee, Sumanta et al. (2010) Delta-like 4 differentially regulates murine CD4 T cell expansion via BMI1. PLoS One 5:e12172|
|Lukacs, Nicholas W; Smit, Joost J; Mukherjee, Sumanta et al. (2010) Respiratory virus-induced TLR7 activation controls IL-17-associated increased mucus via IL-23 regulation. J Immunol 185:2231-9|