TSLP, IL-33, and IL-25: Not just for allergy and helminth infection

Abstract

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, T_H2 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.

Figure 1.. TSLP, IL-33, and IL-25 contribute to both canonical type 2 immunity and diseases not typically associated with type 2.

(A) – (G) Shown is a summary of TSLP (blue square), TSLP receptor (blue receptor), IL-33 (yellow circle), ST2 (yellow receptor), IL-25 (red triangle), IL-25R (red receptor) signaling pathways and the tissues and diseases in which these cytokines have been implicated. These cytokines and their receptors can be grouped based on the transcription factors they activate. When combined with NFAT-inducing signals, these cytokines can activate all the major transcription factors required for lymphocyte survival and function.