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

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(H)2) cells and/or type 2 innate lymphoid cells. Peroxisome proliferator activated receptor-gamma (PPAR-gamma) is typically regarded as an antiinflammatory factor. We report that T(H)2 cells express high levels of PPAR-gamma in response to the allergen house dust mite and after infection with the parasite Heligmosomoides polygyrus. Mice lacking PPAR-gamma in T cells failed to effectively differentiate into IL-5- and IL-13-secreting cells and, hence, did not develop T(H)2 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-gamma in T cells had greatly reduced frequencies of T(H)2 cells in visceral adipose tissue. Mechanistically, PPAR-gamma appeared to promote the expression of the IL-33 receptor on the surface of T(H)2 cells. These results pinpoint PPAR-gamma as a factor that drives type 2 responses in allergy, worm infection, and visceral adipose tissue.