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.
| Ranjan, Ravi; Rani, Asha; Finn, Patricia W et al. (2018) Multiomic Strategies Reveal Diversity and Important Functional Aspects of Human Gut Microbiome. Biomed Res Int 2018:6074918 |
| Turturice, Benjamin A; Ranjan, Ravi; Nguyen, Brian et al. (2017) Perinatal Bacterial Exposure Contributes to IL-13 Aeroallergen Response. Am J Respir Cell Mol Biol 57:419-427 |
| Ranjan, Ravi; Rani, Asha; Metwally, Ahmed et al. (2016) Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing. Biochem Biophys Res Commun 469:967-77 |
| Rani, Asha; Ranjan, Ravi; McGee, Halvor S et al. (2016) A diverse virome in kidney transplant patients contains multiple viral subtypes with distinct polymorphisms. Sci Rep 6:33327 |
| Nakajima, Takeshi; Lin, Ko-Wei; Li, Jinghong et al. (2014) T cells and lung injury. Impact of rapamycin. Am J Respir Cell Mol Biol 51:294-9 |
| Li, Jinghong; Lin, Ko-Wei; Murray, Fiona et al. (2013) Regulation of cytotoxic T lymphocyte antigen 4 by cyclic AMP. Am J Respir Cell Mol Biol 48:63-70 |
| Lin, Ko-Wei; Li, Jinghong; Finn, Patricia W (2011) Emerging pathways in asthma: innate and adaptive interactions. Biochim Biophys Acta 1810:1052-8 |
| Lin, Ko-Wei; Jen, Kai Yu; Suarez, Carlos Jose et al. (2010) Surfactant protein D-mediated decrease of allergen-induced inflammation is dependent upon CTLA4. J Immunol 184:6343-9 |
| Finn, Patricia W; Bigby, Timothy D (2009) Innate immunity and asthma. Proc Am Thorac Soc 6:260-5 |
| Makani, Samir S; Jen, Kai Y; Finn, Patricia W (2008) New costimulatory families: signaling lymphocytic activation molecule in adaptive allergic responses. Curr Mol Med 8:359-64 |
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