IL-4R$α$ signaling in CD4+CD25+FoxP3+ T regulatory cells restrains airway inflammation via limiting local tissue IL-33. Khumalo, J., Kirstein, F., Hadebe, S., & Brombacher, F. JCI Insight, 5(20):e136206, American Society for Clinical Investigation, oct, 2020. ![IL-4R$α$ signaling in CD4+CD25+FoxP3+ T regulatory cells restrains airway inflammation via limiting local tissue IL-33 [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Impaired tolerance to innocuous particles during allergic asthma has been linked to the increased plasticity of FoxP3+ regulatory T (Treg) cells, reprogramming into pathogenic effector cells, thus exacerbating airway disease. Failure in tolerance is suggested to be driven by TH2 inflammatory signals. The canonical IL-4R$α$-signalling, an essential driver of TH2-type airway responses to allergens was investigated on its in vivo role on the regulatory function of FoxP3+ Tregs in allergic asthma. We used transgenic Foxp3creIL-4r$α$-/lox and littermate control mice to investigate the role of IL-4/IL-13 signalling via T regs in a house dust mite (HDM)-induced allergic airway disease. We sensitised mice intratracheally on day 0 and challenged them on day 6-10 and analysed airway hyperresponsiveness (AHR), airway inflammation, mucus production and cellular profile on day 14. In the absence of IL-4R$α$ responsiveness on FoxP3+ Tregs, there was an exacerbated AHR and airway inflammation in HDM-sensitised mice. Interestingly, a reduced induction of FoxP3+ Tregs accompanied increased IL-33 “alarmin” production and innate lymphoid cells type 2 (ILC2) activation in the lung exacerbating airway hyperreactivity and lung eosinophilia. We conclude that IL-4R$α$ unresponsive FoxP3+ T regulatory cells results in exaggerated innate TH2-type, IL-33-dependent airway inflammation and a break in tolerance during allergic asthma.
@article{Khumalo2020,
abstract = {Impaired tolerance to innocuous particles during allergic asthma has been linked to the increased plasticity of FoxP3+ regulatory T (Treg) cells, reprogramming into pathogenic effector cells, thus exacerbating airway disease. Failure in tolerance is suggested to be driven by TH2 inflammatory signals. The canonical IL-4R$\alpha$-signalling, an essential driver of TH2-type airway responses to allergens was investigated on its in vivo role on the regulatory function of FoxP3+ Tregs in allergic asthma. We used transgenic Foxp3creIL-4r$\alpha$-/lox and littermate control mice to investigate the role of IL-4/IL-13 signalling via T regs in a house dust mite (HDM)-induced allergic airway disease. We sensitised mice intratracheally on day 0 and challenged them on day 6-10 and analysed airway hyperresponsiveness (AHR), airway inflammation, mucus production and cellular profile on day 14. In the absence of IL-4R$\alpha$ responsiveness on FoxP3+ Tregs, there was an exacerbated AHR and airway inflammation in HDM-sensitised mice. Interestingly, a reduced induction of FoxP3+ Tregs accompanied increased IL-33 “alarmin” production and innate lymphoid cells type 2 (ILC2) activation in the lung exacerbating airway hyperreactivity and lung eosinophilia. We conclude that IL-4R$\alpha$ unresponsive FoxP3+ T regulatory cells results in exaggerated innate TH2-type, IL-33-dependent airway inflammation and a break in tolerance during allergic asthma.},
author = {Khumalo, Jermaine and Kirstein, Frank and Hadebe, Sabelo and Brombacher, Frank},
doi = {10.1172/jci.insight.136206},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Khumalo et al. - 2020 - IL-4R$\alpha$ signaling in CD4CD25FoxP3 T regulatory cells restrains airway inflammation via limiting local tissue IL-3.pdf:pdf},
issn = {2379-3708},
journal = {JCI Insight},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {oct},
number = {20},
pages = {e136206},
pmid = {32931477},
publisher = {American Society for Clinical Investigation},
title = {{IL-4R$\alpha$ signaling in CD4+CD25+FoxP3+ T regulatory cells restrains airway inflammation via limiting local tissue IL-33}},
url = {https://doi.org/10.1172/jci.insight.136206},
volume = {5},
year = {2020}
}
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We used transgenic Foxp3creIL-4r$α$-/lox and littermate control mice to investigate the role of IL-4/IL-13 signalling via T regs in a house dust mite (HDM)-induced allergic airway disease. We sensitised mice intratracheally on day 0 and challenged them on day 6-10 and analysed airway hyperresponsiveness (AHR), airway inflammation, mucus production and cellular profile on day 14. In the absence of IL-4R$α$ responsiveness on FoxP3+ Tregs, there was an exacerbated AHR and airway inflammation in HDM-sensitised mice. Interestingly, a reduced induction of FoxP3+ Tregs accompanied increased IL-33 “alarmin” production and innate lymphoid cells type 2 (ILC2) activation in the lung exacerbating airway hyperreactivity and lung eosinophilia. 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