Initiation of type 2 immunity at barrier surfaces

Although seemingly unrelated, parasitic worms, venoms, and allergens all induce a type 2 immune response. The effector functions and clinical features of type 2 immunity are well-defined, but fundamental questions about the initiation of type 2 immunity remain unresolved. How are these enormously diverse type 2 stimuli first detected? How are type 2 helper T cells primed and regulated? And how do mechanisms of type 2 initiation vary across tissues? Here, we review the common themes governing type 2 immune sensing and explore aspects of T cell priming and effector reactivation that make type 2 helper T cells a unique T helper lineage. Throughout the review, we emphasize the importance of non-hematopoietic cells and highlight how the unique anatomy and physiology of each barrier tissue shape mechanisms of type 2 immune initiation.