PPARγ in Dendritic Cells and T Cells Drives Pathogenic Type-2 Effector Responses in Lung Inflammation

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2017 Aug 12

PMID 28798029

Citations 65

Authors

Samuel Philip Nobs

Sara Natali

Lea Pohlmeier

Katarzyna Okreglicka

Christoph Schneider

Michael Kurrer

Federica Sallusto

Manfred Kopf

Affiliations

Soon will be listed here.

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 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.

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