The release of cytokines from epithelial and stromal cells is critical for the initiation and maintenance of tissue immunity. Three such cytokines, thymic stromal lymphopoietin, IL-33, and IL-25, are important regulators of type 2 immune responses triggered by parasitic worms and allergens. In particular, these cytokines activate group 2 innate lymphoid cells, TH2 cells, and myeloid cells, which drive hallmarks of type 2 immunity. However, emerging data indicate that these tissue-associated cytokines are not only involved in canonical type 2 responses but are also important in the context of viral infections, cancer, and even homeostasis. Here, we provide a brief review of the roles of thymic stromal lymphopoietin, IL-33, and IL-25 in diverse immune contexts, while highlighting their relative contributions in tissue-specific responses. We also emphasize a biologically motivated framework for thinking about the integration of multiple immune signals, including the 3 featured in this review.
Keywords: Cytokines; allergy; cancer; helminth; tissue immunity; viral infection.
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