PPAR? in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation.

ABSTRACT: 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 PPAR? is known to promote M2-macrophage and alveolar macrophage development. Here, we report that PPAR? 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 PPAR? 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 PPAR? in lung-resident CD11b+ DCs, which enhances migration to draining lymph nodes and Th2 priming capacity. Thus, we uncover a surprising proinflammatory role for PPAR? and establish it as a novel, important mediator of DC-T cell interactions in type-2 immunity.

SUBMITTER: Nobs SP 

PROVIDER: S-EPMC5626395 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature