CD4 T Cell Motility in Inflamed Tissues
Cell migration is determined by the cell-intrinsic machinery for motility such as integrins, actin regulators and chemokine receptors and by the extrinsic composition of the extracellular matrix. The way in which effector CD4 T cells navigate through inflamed interstitial tissue at sites of infection is not well understood.
We are using imaging techniques to define the molecular requirements for interstitial movement focusing on the role of integrins and their interaction with distinct matrix components and the dynamic expression of chemokine receptors for response to chemokine gradients. We predict that the density and composition of chemotactic and matrix components will be modified by different types of inflammation and will dictate the migratory machinery required by the incoming effector T cells.
Using intra-vital 2-photon microscopy we have already revealed interesting differences between Th1 and Th2 cells in the mode of motility in inflamed tissue. Transcriptional analysis revealed that the differences in movement are driven by intrinsic differences in the cells themselves.
Our overall goal is to define mechanistic control points for T cell surveillance within functionally distinct sites of inflammation. In the long-term, identification of diverse requirements for T cell function will lead to the selective therapeutic targeting of specific tissues or pathologies.
Overstreet, Gaylo et al 2013 Nature Immunology
Gaylo-Moynihan, Prizant et al 2019 Immunity
Fowell & Kim 2021 Nature Reviews Immunology