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Comment
. 2020 Nov;21(11):1313-1314.
doi: 10.1038/s41590-020-0797-z.

Wnt and Hippo pathways in regulatory T cells: a NOTCH above in asthma

Hamida Hammad  1   2 , Bart N Lambrecht  3   4   5
Affiliations
Comment

Wnt and Hippo pathways in regulatory T cells: a NOTCH above in asthma

Hamida Hammad et al. Nat Immunol. 2020 Nov.

Abstract

The activation of the Notch4-Wnt-GDF15 axis in induced Tregs dampens their immunoregulatory function and turns them into Th2 and Th17 cytokine producers, allowing them to maintain ongoing allergic asthma.

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Figures

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.
See this image and copyright information in PMC

Comment on

  • A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma.
    Harb H, Stephen-Victor E, Crestani E, Benamar M, Massoud A, Cui Y, Charbonnier LM, Arbag S, Baris S, Cunnigham A, Leyva-Castillo JM, Geha RS, Mousavi AJ, Guennewig B, Schmitz-Abe K, Sioutas C, Phipatanakul W, Chatila TA. Harb H, et al. Nat Immunol. 2020 Nov;21(11):1359-1370. doi: 10.1038/s41590-020-0777-3. Epub 2020 Sep 14. Nat Immunol. 2020. PMID: 32929274 Free PMC article.

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