Spatiotemporal Control of Effector Function in Infected Tissues
The molecular control of CD4 differentiation into functionally distinct effector lineages has been extensively studied but the fate of the effector T cells once they leave the lymph node is less well understood. We are interested in how the inflammatory milieu at sites of infection and autoimmune attack may modify the effector function of CD4+ T cells.
Our main hypothesis is that while CD4 T cells may be programmed for function in the lymph node, the efficiency of executing that function will be controlled by the type and extent of inflammation at the pathogenic site. Function may be modified by the degree of recruitment or retention in the tissue, provision of the signals required to support high level cytokine production and/or reprogramming in light of the potential for functional plasticity.
Our previous work with Leishmania major revealed the functional editing of the available cytokine repertoire at the infection site. We use advanced imaging techniques to visualize defined effector populations within inflamed tissue and their interaction with antigen-bearing cells. The ear dermis provides a tractable site for intra-vital 2-photon microscopy and fluorescent tags on effector cells, Tregs and Leishmania enable the analysis of spatially distinct cellular interactions.
Current studies utilize optogenetic approaches to mark effector T cells in time and space. Initial transcriptomic studies (RNAseq) have revealed temporal changes in Th1 gene programs following entry and exit of the inflamed skin.
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