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

Ting Chen; Christopher A Tibbitt; Xiaogang Feng; Julian M Stark; Leona Rohrbeck; Lisa Rausch; Saikiran K Sedimbi; Mikael C I Karlsson; Bart N Lambrecht; Gunilla B Karlsson Hedestam; Rudi W Hendriks; Benedict J Chambers; Susanne Nylén; Jonathan M Coquet

doi:10.1126/sciimmunol.aal5196

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

Sci Immunol. 2017 Mar 10;2(9):eaal5196. doi: 10.1126/sciimmunol.aal5196.

Authors

Affiliations

¹ Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
² Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent 9052B, Belgium.
³ Department of Respiratory Medicine, Ghent University Hospital, Ghent 9000, Belgium.
⁴ Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
⁵ Department of Medicine, Center for Infectious Medicine, F59, Karolinska Institute, Karolinska University Hospital Huddinge, Huddinge, Sweden.
⁶ Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden. jonathan.coquet@ki.se.

PMID: 28783701
DOI: 10.1126/sciimmunol.aal5196

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 (T_H2) 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 T_H2 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 T_H2 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 T_H2 cells in visceral adipose tissue. Mechanistically, PPAR-γ appeared to promote the expression of the IL-33 receptor on the surface of T_H2 cells. These results pinpoint PPAR-γ as a factor that drives type 2 responses in allergy, worm infection, and visceral adipose tissue.