Tissues and organs of the mammalian body are shaped and maintained by mainly three structural cell types. Endothelial cells form blood vessels and control access of metabolites and migration of cells to tissues; epithelial cells form barriers around tissues, organs and the body to isolate inside from outside; and fibroblasts provide the connective layers that support tissues and organs structurally. The lab of Christoph Bock performed a pioneering comparative analysis of structural cells in twelve mouse organs under homeostatic conditions and in response to systemic cytokine and viral challenges and found that in specific contexts these cell types contribute to immune regulation and defence. Importantly, epigenome and transcription profiling identified JAK-STAT as important mediators of the organ-specific immune responses in structural types.