Antigen presenting cells (APCs) are crucial mediators between innate and adaptive immunity, translating information regarding bodily insults into durable and appropriate immune responses with the goal of restoring tissue homeostasis. The ability to mount numerous types of responses tailored to address a variety of diverse insults reveals heterogeneity among tissue APCs. The studies in this thesis address the signals that tissue APCs receive, how they integrate those signals, and how they propagate type 2 allergic lung inflammation, which can be a driving force in asthma. To this end, we first identify a process by which IL-33, a cytokine implicated in type 2 inflammation, stimulates the production of chemokines which attract allergen-bearing monocytes to the lung parenchyma during allergen challenge. Monocyte migration to the lung parenchyma during allergen exposure plays an important role in coordinating subsequent tissue eosinophilia, but not in promoting T cell responses to allergen. Instead, allergic T cell responses are driven by lung dendritic cells (DCs). We detail mechanisms by which interferon regulatory factor 4 (IRF4) promotes the migration of lung DCs to the lymph nodes and the expression of downstream factors that promote the education of T helper type 2 (Th2) cells. These IRF4-dependent processes are critical for promoting type 2 responses during allergic sensitization and during the effector response, but are not continuously essential for resident memory T cells (TRM cells) to mount memory responses. Finally, we investigate additional roles for IRF4-expressing DCs during intestinal infection with a colitis-inducing pathogen, suggesting that IRF4-expressing DCs also mediate Th22 responses in the gut. Together, these studies define novel mechanisms by which specific tissue APCs promote tailored responses to insults at mucosal barriers.



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