Asthma incidence is increasing and warrants investigation of distinct immune mechanisms. Innate, non- antigen-dependent immunity has been shown to play a role in allergic responses. Our data suggest that the innate immune collectin, surfactant (SP-)-D, can function as an endogenous, anti-inflammatory regulator of allergic responses. We analyze T cell and SP-D interactions, and focus on T helper (Th) 17 T cells. Also, we investigate evidence that cytotoxic t-lymphocyte antigen 4 (CTLA4), an inhibitor of T cells, mediates SP-D effects. Our data indicate that SP-D diminishes IL-17 responses while increasing CTLA4. Our overall hypothesis is that SP-D is an endogenous regulator of immunity that decreases allergic inflammation by inducing immunosuppressive pathways within T cells.
Aim 1 will investigate the mechanisms of SP-D modulation of T cell subsets.
Aim 2 will analyze the biochemical and cellular mechanisms of SP-D binding to T cells.
Aim 3 will focus on SP-D-dependent molecular mechanisms regulating CTLA4 expression.
Aim 4 will investigate the response of T cell subsets to SP-D in cells obtained from asthmatic subjects. An anti-inflammatory role for SP-D, specifically in T cell activation, reveals a distinct pathway for potential therapeutic intervention in T cell mediated disorders. This proposal will examine biochemical and biological pathways that may lead to the development of candidates for therapeutic intervention for asthma.
Allergic asthma has become an epidemic in many parts of the world, and compels investigation of alternative strategies. We will focus on immune pathways that are not classically associated with asthma, but may uncover new insights into the prevention or treatment of asthma. We will examine the roles of immune molecule in decreasing immune responses, including immune (T cell) activation in an animal model of asthma and with samples from human asthmatics.
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