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. Author manuscript; available in PMC: 2021 May 31.
Published in final edited form as: Nat Immunol. 2020 Nov 1;21(11):1313–1314. doi: 10.1038/s41590-020-0797-z

Figure 1.

Figure 1

Notch4+ regulatory T cells contribute to Th2 immunity to allergens and air pollutants. Following uptake of ultrafine particles, alveolar macrophages release high amounts of IL-6, which promotes Notch4 expression on induced regulatory T cells. Notch4 signaling leads to the activation of the Hippo and of the Wnt pathway. Both pathways are sufficient to shift regulatory T cells away from immunoregulation. Instead, the Wnt and Hippo pathways activate a Th2 and Th17 program in Notch4+ regulatory T cells. In addition, the Wnt pathway allows GDF-15 release by these cells, and GDF-15 triggers IL-13 release by ILC2. The cytokine milieu induced by Notch4+ regulatory T cells allows asthma feature to develop and to maintain.