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A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma
Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that IL-6 and STAT3 transcription factor-dependent upregulation of Notch4 receptor on Iung tissue regulatory T (T(reg)) cells is necessary for allergens and particulate matter pollutants to p...
| Autores principales: | , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578174/ https://www.ncbi.nlm.nih.gov/pubmed/32929274 http://dx.doi.org/10.1038/s41590-020-0777-3 |
| _version_ | 1783598309049368576 |
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| author | Harb, Hani Stephen-Victor, Emmanuel Crestani, Elena Benamar, Mehdi Massoud, Amir Cui, Ye Charbonnier, Louis-Marie Arbag, Sena Baris, Safa Cunnigham, Amparito Leyva-Castillo, Juan Manuel Geha, Raif S. Mousavi, Amirhosein J. Guennewig, Boris Schmitz-Abe, Klaus Sioutas, Constantinos Phipatanakul, Wanda Chatila, Talal A. |
| author_facet | Harb, Hani Stephen-Victor, Emmanuel Crestani, Elena Benamar, Mehdi Massoud, Amir Cui, Ye Charbonnier, Louis-Marie Arbag, Sena Baris, Safa Cunnigham, Amparito Leyva-Castillo, Juan Manuel Geha, Raif S. Mousavi, Amirhosein J. Guennewig, Boris Schmitz-Abe, Klaus Sioutas, Constantinos Phipatanakul, Wanda Chatila, Talal A. |
| author_sort | Harb, Hani |
| collection | PubMed |
| description | Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that IL-6 and STAT3 transcription factor-dependent upregulation of Notch4 receptor on Iung tissue regulatory T (T(reg)) cells is necessary for allergens and particulate matter pollutants to promote airway inflammation. Notch4 subverted T(reg) cells into T(H)2 and T(H)17 effector T (T(eff)) cells by Wnt and Hippo pathway-dependent mechanisms. Wnt activation induced growth and differentiation factor 15 (GDF15) expression in T(reg) cells, which activated group 2 innate lymphoid cells (ILC2) to provide a feed-forward mechanism for aggravated inflammation. Notch4, Wnt and Hippo were upregulated on circulating T(reg) cells of asthmatics as a function of disease severity, in association with reduced T(reg) cell-mediated suppression. Our studies thus identify Notch4-mediated immune tolerance subversion as a fundamental mechanism that licenses tissue inflammation in asthma. |
| format | Online Article Text |
| id | pubmed-7578174 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-75781742021-03-14 A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma Harb, Hani Stephen-Victor, Emmanuel Crestani, Elena Benamar, Mehdi Massoud, Amir Cui, Ye Charbonnier, Louis-Marie Arbag, Sena Baris, Safa Cunnigham, Amparito Leyva-Castillo, Juan Manuel Geha, Raif S. Mousavi, Amirhosein J. Guennewig, Boris Schmitz-Abe, Klaus Sioutas, Constantinos Phipatanakul, Wanda Chatila, Talal A. Nat Immunol Article Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that IL-6 and STAT3 transcription factor-dependent upregulation of Notch4 receptor on Iung tissue regulatory T (T(reg)) cells is necessary for allergens and particulate matter pollutants to promote airway inflammation. Notch4 subverted T(reg) cells into T(H)2 and T(H)17 effector T (T(eff)) cells by Wnt and Hippo pathway-dependent mechanisms. Wnt activation induced growth and differentiation factor 15 (GDF15) expression in T(reg) cells, which activated group 2 innate lymphoid cells (ILC2) to provide a feed-forward mechanism for aggravated inflammation. Notch4, Wnt and Hippo were upregulated on circulating T(reg) cells of asthmatics as a function of disease severity, in association with reduced T(reg) cell-mediated suppression. Our studies thus identify Notch4-mediated immune tolerance subversion as a fundamental mechanism that licenses tissue inflammation in asthma. 2020-09-14 2020-11 /pmc/articles/PMC7578174/ /pubmed/32929274 http://dx.doi.org/10.1038/s41590-020-0777-3 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Harb, Hani Stephen-Victor, Emmanuel Crestani, Elena Benamar, Mehdi Massoud, Amir Cui, Ye Charbonnier, Louis-Marie Arbag, Sena Baris, Safa Cunnigham, Amparito Leyva-Castillo, Juan Manuel Geha, Raif S. Mousavi, Amirhosein J. Guennewig, Boris Schmitz-Abe, Klaus Sioutas, Constantinos Phipatanakul, Wanda Chatila, Talal A. A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma |
| title | A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma |
| title_full | A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma |
| title_fullStr | A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma |
| title_full_unstemmed | A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma |
| title_short | A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma |
| title_sort | regulatory t cell notch4-gdf15 axis licenses tissue inflammation in asthma |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578174/ https://www.ncbi.nlm.nih.gov/pubmed/32929274 http://dx.doi.org/10.1038/s41590-020-0777-3 |
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