Lung inflammatory diseases such as allergic asthma affects almost 300 million people worldwide, with up to 11% of the population of the United States alone and its rate continues to increase in urbanized countries. This disease cannot be cured, making it one of the most expensive diseases for healthcare systems in developed countries. This makes this work highly significant. Allergic asthma is characterized by a balance of inflammatory cytokines such as those produced by Th2 and Th17 cells, and counter regulation of these cells Foxp3+ T regulatory cells (Treg) and IL10+ Type 1 regulatory T cells. While much is known about Tregs, very little is know about the intracellular signals that regulate Tr1 cell development and function. Being able to manipulate the suppression mediated by Tr1 cells is a potentially promising immunotherapeutic strategy for controlling and suppressing such lung inflammation. We have found that tyrosine kinase Itk regulates the development of Tr1 cells. Based on our results, we have developed the hypothesis that Itk regulates the development and function of Tr1 cells during lung inflammation. We propose experiments in two specific aims that will determine the role of Itk in the development and function of Tr1 cells in mice and human, and mechanism by which it does so. This work is extremely innovative as we utilize novel and unique transgenic mice and approaches, and have exciting preliminary data that when fleshed out, will provide information on a signaling pathway that could be used to manipulate the development and function of Tr1 cells during lung inflammation as well as other inflammatory conditions.
Lung inflammation afflicts an increasing number of Americans but the underlying cause is unclear. This lack of clarity manifests in the fact that current treatment do not cure these diseases. The T helper response is involved in the development of this disease, with their production of inflammatory cytokines contributing to the symptoms. Type 1 regulatory T cells are able to suppress these T helper responses that lead to lung inflammation, but we do not understand the molecular basis for how these cells develop, or what pathways control their function. This work will examine a signaling pathway that is pharmaceutically tractable, to determine its role in the development and function of Type 1 regulatory T cells, and may suggest methods to better control lung inflammation by these cells.
| Huang, Weishan; Solouki, Sabrina; Carter, Chavez et al. (2018) Beyond Type 1 Regulatory T Cells: Co-expression of LAG3 and CD49b in IL-10-Producing T Cell Lineages. Front Immunol 9:2625 |
| August, Avery (2018) Who regulates whom: ZNF341 is an additional player in the STAT3/TH17 song. Sci Immunol 3: |
| Martinez, Luis R; Boucaud, Dwayne W; Casadevall, Arturo et al. (2018) Factors Contributing to the Success of NIH-Designated Underrepresented Minorities in Academic and Nonacademic Research Positions. CBE Life Sci Educ 17:ar32 |
