Tamar Lea Ben Shaanan, PhD, Postdoctoral Fellow University of California, San Francisco The lung and respiratory system are the principal interface with the inhaled environment. Protecting this barrier site are cells of the immune system. Lung classical dendritic cells (cDCs) can be activated by inhaled molecules and, depending on context, stimulate a response. Lung cDC positioning is functionally critical, yet the relevant guidance cues are not fully understood. Dr. Ben Shaanan’s project aims to explore the impact of two different factors in determining lung cDCs positioning. The first is the chemoattractant receptor EBI2 and its ligands. While their role in controlling cDC localization in the spleen have been established, here she proposes to test their impact on lung cDC positioning and homeostasis. She will then use conditional knockout mice to confirm that the lung cDC2 deficiency detected in EBI2 null mice reflects an action intrinsically in cDCs. By using deep tissue imaging of fluorescent reporter mice, she will define the EBI2-dependent cDC2 niche. She will use conditional deletion of EBI2 ligand producing enzymes to determine the relevant cell types. The second factor that Dr. Ben Shaanan’s project explores is the connection between peptidergic nociceptors and lung cDCs. While such connections have been documented in the skin, there is limited understanding of how these innervations impact lung cDCs. Complementary selective neuronal activation and ablation techniques in mice will allow her to test for altered cDC positioning, homeostasis, and function. Taken together, given the important role of lung cDCs in shaping immunity, the results can improve our understanding of the cellular dynamics underlying lung cell positioning, antigen sensing, and immunity. Projects and Grants Role of EBI2 and sensory neurons in lung dendritic cell homeostasis and function University of California, San Francisco | All Cancers | 2022 | Jason Cyster, Ph.D.
