Research ArticleALLERGY

PPAR-γ promotes type 2 immune responses in allergy and nematode infection

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Science Immunology  10 Mar 2017:
Vol. 2, Issue 9, eaal5196
DOI: 10.1126/sciimmunol.aal5196

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Type 2 immunity on PPAR

Agonists to the anti-inflammatory molecule peroxisome proliferator activated receptor–γ (PPAR-γ) decrease airway inflammation in animal models but have had limited success in clinical trials. Now, Chen et al. examine the contribution of PPAR-γ to T helper type 2 (TH2) immunity, which is critical for both allergy and parasite immune response. Mice that lacked PPAR-γ did not develop allergic pathology and failed to protect against nematode infection. These mice lacked interleukin-5 (IL-5)– and IL-13–secreting cells and had reduced frequencies of TH2 cells in visceral adipose tissue. PPAR-γ agonists up-regulated the IL-33 receptor ST2. Hence, PPAR-γ may contribute to IL-5 and IL-13 production by TH2 cells, which highlights the need for caution in using PPAR-γ agonists for TH2-mediated diseases.

Abstract

A hallmark of immunity to worm infections and many allergies is a strong type 2 immune response. This is characterized by the production of cytokines interleukin-5 (IL-5) and IL-13 by adaptive T helper 2 (TH2) cells and/or type 2 innate lymphoid cells. Peroxisome proliferator activated receptor–γ (PPAR-γ) is typically regarded as an anti-inflammatory factor. We report that TH2 cells express high levels of PPAR-γ in response to the allergen house dust mite and after infection with the parasite Heligmosomoides polygyrus. Mice lacking PPAR-γ in T cells failed to effectively differentiate into IL-5– and IL-13–secreting cells and, hence, did not develop TH2 cell–associated pathologies, including goblet cell metaplasia and eosinophilia, in response to allergen challenge. Furthermore, these mice could not mount protective immune responses to nematode infection. In addition, mice lacking PPAR-γ in T cells had greatly reduced frequencies of TH2 cells in visceral adipose tissue. Mechanistically, PPAR-γ appeared to promote the expression of the IL-33 receptor on the surface of TH2 cells. These results pinpoint PPAR-γ as a factor that drives type 2 responses in allergy, worm infection, and visceral adipose tissue.

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