Regulation of T cell activation, differentiation, and regulation of inflammation, anti inflammation, and memory development by Tec family kinases
Itk is a member of the Tec family of tyrosine kinases that is activated downstream of the T cell receptor. This kinase is able to regulate processes involved in T-cell development and T cell differentiation. Understanding the specific downstream activities of these kinases is crucial to understanding how they impact lymphoid activation and development. We explore the signaling pathways regulated by Tec family kinases that regulate the differentiation and function of Th1, Th2, Th17, and Foxp3+ and Foxp3- Type 1 regulatory T cells. Our work has shown that manipulating the activity of Itk can tune the development of Th17 and Foxp3+ regulatory T cells, and we continue to explore the fundamental mechanisms of this tuning.
We also explore these signaling pathways in the development of CD8+ T cell memory in response to infection, as well as other immune processes. For example, we have shown that both antigen affinity, and T cell receptor mediated Itk signals can independently tune the timing of the development of CD8+ memory T cells during bacterial infection.
We are particularly interested in how Itk mediated signals tune the response of T cells in lung inflammatory diseases, including during mouse models of influenza and SARS-CoV-2 infection, allergic airway allergy inflammation and hypersensitivity pneumonitis. Recent work from the lab includes showing that the adaptive immune cells (B and T cells) are required for the development of pathology during SARS-CoV-2 infection, and that age dependent exposure to diverse microbial antigens has differential effect on the development of allergic airway inflammation.