IL-4Rα signaling in CD4 CD25 FoxP3 T regulatory cells restrains airway inflammation via limiting local tissue IL-33
Division of Immunology and ICGEB researchers Dr Jermaine Khumalo, Dr Frank Kirstein, Dr Sabelo Hadebe and Professor Frank Brombacher, recently authored a paper in JCI Insight. The paper published in September 2020 is entitled “IL-4Rα signaling in CD4+CD25+FoxP3+ T regulatory cells restrains airway inflammation via limiting local tissue IL-33”.
“Impaired tolerance to innocuous particles during allergic asthma has been linked to increased plasticity of FoxP3+ regulatory T cells (Tregs) reprogramming into pathogenic effector cells, thus exacerbating airway disease. However, failure of tolerance mechanisms is driven by Th2 inflammatory signals”.
The Division of Immunology and International Centre for Genetic Engineering and Biotechnology (ICGEB) researchers explored the “in vivo role of canonical IL-4 receptor α (IL-4Rα) signaling, an essential driver of Th2-type airway responses to allergens, on the regulatory function of FoxP3+Tregs in allergic asthma”.
The researchers showed that the absence of IL-4Rα responsiveness on FoxP3+Tregs exacerbated airway hyperreactivity and airway inflammation in HDM-sensitized mice.
The “reduced induction of FoxP3+ Tregs accompanied increased IL-33 production and type 2 innate lymphoid cell activation in the lung.”
Taken together, the researchers’ findings indicate that IL-4Rα–unresponsive FoxP3+ Tregs result in exaggerated innate type 2, IL-33–dependent airway inflammation and a break in tolerance during allergic asthma.
Dr Hadebe and Prof Brombacher share senior authorship while Dr Khumalo has since moved to the Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA, for a postdoctoral fellowship with Dr. Gregory Seumois, after defending his PhD earlier in 2020.
Read the paper - IL-4Rα signaling in CD4+CD25+FoxP3+ T regulatory cells restrains airway inflammation via limiting local tissue IL-33
Article by Bonamy Holtak