The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease
Foxa2, a member of the Forkhead box (Fox) family of transcription factors, plays an important role in the regulation of lung function and lung tissue homeostasis. FOXA2 expression is reduced in the lung and airways epithelium of asthmatic patients and in mice absence of Foxa2 from the lung epitheliu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.890781/full |
| _version_ | 1798041122957688832 |
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| author | Diana C. Yánez Diana C. Yánez Ching-In Lau Eleftheria Papaioannou Mira M. Chawda Jasmine Rowell Susan Ross Anna Furmanski Anna Furmanski Tessa Crompton |
| author_facet | Diana C. Yánez Diana C. Yánez Ching-In Lau Eleftheria Papaioannou Mira M. Chawda Jasmine Rowell Susan Ross Anna Furmanski Anna Furmanski Tessa Crompton |
| author_sort | Diana C. Yánez |
| collection | DOAJ |
| description | Foxa2, a member of the Forkhead box (Fox) family of transcription factors, plays an important role in the regulation of lung function and lung tissue homeostasis. FOXA2 expression is reduced in the lung and airways epithelium of asthmatic patients and in mice absence of Foxa2 from the lung epithelium contributes to airway inflammation and goblet cell hyperplasia. Here we demonstrate a novel role for Foxa2 in the regulation of T helper differentiation and investigate its impact on lung inflammation. Conditional deletion of Foxa2 from T-cells led to increased Th2 cytokine secretion and differentiation, but decreased Th1 differentiation and IFN-γ expression in vitro. Induction of mouse allergic airway inflammation resulted in more severe disease in the conditional Foxa2 knockout than in control mice, with increased cellular infiltration to the lung, characterized by the recruitment of eosinophils and basophils, increased mucus production and increased production of Th2 cytokines and serum IgE. Thus, these experiments suggest that Foxa2 expression in T-cells is required to protect against the Th2 inflammatory response in allergic airway inflammation and that Foxa2 is important in T-cells to maintain the balance of effector cell differentiation and function in the lung. |
| first_indexed | 2024-04-11T22:17:06Z |
| format | Article |
| id | doaj.art-411a3068191e427ea24ae234c254d6a4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T22:17:06Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-411a3068191e427ea24ae234c254d6a42022-12-22T04:00:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.890781890781The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway DiseaseDiana C. Yánez0Diana C. Yánez1Ching-In Lau2Eleftheria Papaioannou3Mira M. Chawda4Jasmine Rowell5Susan Ross6Anna Furmanski7Anna Furmanski8Tessa Crompton9UCL Great Ormond Street Institute of Child Health, London, United KingdomSchool of Medicine, Universidad San Francisco de Quito, Quito, EcuadorUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomSchool of Life Sciences, University of Bedfordshire, Luton, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomFoxa2, a member of the Forkhead box (Fox) family of transcription factors, plays an important role in the regulation of lung function and lung tissue homeostasis. FOXA2 expression is reduced in the lung and airways epithelium of asthmatic patients and in mice absence of Foxa2 from the lung epithelium contributes to airway inflammation and goblet cell hyperplasia. Here we demonstrate a novel role for Foxa2 in the regulation of T helper differentiation and investigate its impact on lung inflammation. Conditional deletion of Foxa2 from T-cells led to increased Th2 cytokine secretion and differentiation, but decreased Th1 differentiation and IFN-γ expression in vitro. Induction of mouse allergic airway inflammation resulted in more severe disease in the conditional Foxa2 knockout than in control mice, with increased cellular infiltration to the lung, characterized by the recruitment of eosinophils and basophils, increased mucus production and increased production of Th2 cytokines and serum IgE. Thus, these experiments suggest that Foxa2 expression in T-cells is required to protect against the Th2 inflammatory response in allergic airway inflammation and that Foxa2 is important in T-cells to maintain the balance of effector cell differentiation and function in the lung.https://www.frontiersin.org/articles/10.3389/fimmu.2022.890781/fullFoxa2ShhTh2 airway inflammationTh1Th2 |
| spellingShingle | Diana C. Yánez Diana C. Yánez Ching-In Lau Eleftheria Papaioannou Mira M. Chawda Jasmine Rowell Susan Ross Anna Furmanski Anna Furmanski Tessa Crompton The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease Frontiers in Immunology Foxa2 Shh Th2 airway inflammation Th1 Th2 |
| title | The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease |
| title_full | The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease |
| title_fullStr | The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease |
| title_full_unstemmed | The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease |
| title_short | The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease |
| title_sort | pioneer transcription factor foxa2 modulates t helper differentiation to reduce mouse allergic airway disease |
| topic | Foxa2 Shh Th2 airway inflammation Th1 Th2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.890781/full |
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