PPARγ in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation

• DOI: 10.1084/jem.20162069
• Publication Date: 2017-08-10T14:10:16Z
• Authors: Samuel Philip Nobs; Sara Natali; Lea Pohlmeier; Katarzyna Okreglicka; Christoph Schneider; Michael Kurrer; Federica Sallusto; Manfred Kopf
• Keywords: Mice, Knockout; Immunity, Cellular; 0303 health sciences; T-Lymphocytes; Dendritic Cells; Pneumonia; Flow Cytometry; Interleukin-33; 3. Good health; Mice, Inbred C57BL; PPAR gamma; Disease Models, Animal; Mice; 03 medical and health sciences; Th2 Cells; Animals; Interleukin-4; Research Articles

Type-2 immune responses are well-established drivers of chronic inflammatory diseases, such as asthma, and represent a large burden on public health systems. The transcription factor PPARγ is known to promote M2-macrophage and alveolar macrophage development. Here, we report that PPARγ plays a key role in both T cells and dendritic cells (DCs) for development of type-2 immune responses. It is predominantly expressed in mouse Th2 cells in vitro and in vivo as well as human Th2 cells from allergic patients. Using conditional knockouts, we show that PPARγ signaling in T cells, although largely dispensable for IL-4 induction, is critical for IL-33–driven Th2 effector function in type-2 allergic airway responses. Furthermore, we demonstrate that IL-4 and IL-33 promote up-regulation of PPARγ in lung-resident CD11b+ DCs, which enhances migration to draining lymph nodes and Th2 priming capacity. Thus, we uncover a surprising proinflammatory role for PPARγ and establish it as a novel, important mediator of DC–T cell interactions in type-2 immunity.