The pioneer transcription factor Foxa2 modulates T helper differentiation to reduce mouse allergic airway disease
Authors
Yánez, Diana C.Lau, Ching-In
Papaioannou, Eleftheria
Chawda, Mira Manilal
Rowell, Jasmine
Ross, Susan
Furmanski, Anna L.
Crompton, Tessa
Affiliation
UCL Great Ormond Street Institute of Child HealthUniversidad San Francisco de Quito
University of Bedfordshire
Issue Date
2022-08-08
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Show full item recordAbstract
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.Citation
Yánez DC, Lau CI, Papaioannou E, Chawda MM, Rowell J, Ross S, Furmanski A, Crompton T (2022) 'The pioneer transcription factor Foxa2 modulates T helper differentiation to reduce mouse allergic airway disease', Frontiers in Immunology, 13 (890781)Publisher
FrontiersJournal
Frontiers in ImmunologyPubMed ID
36003391PubMed Central ID
PMC9393229Additional Links
https://www.frontiersin.org/articles/10.3389/fimmu.2022.890781/fullhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393229/
Type
ArticleLanguage
enISSN
1664-3224EISSN
1664-3224Sponsors
This work was supported by grants from the MRC, BBSRC and GOSHCCae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2022.890781
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