ArticlePLoS biology2018
The Foxp3+ regulatory T-cell population requires IL-4Rα signaling to control inflammation during helminth infections.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Steroid receptor coactivator 3-deficient regulatory T cells eradicate multiple solid tumors in syngeneic mouse models.Oncoimmunology · 2026Article
- Type 2 conventional dendritic cells and regulatory T cells form a barrier tissue circuit to control allergic inflammation.bioRxiv : the preprint server for biology · 2026Article
- Review
- Deciphering the developmental trajectory of tissue-resident Foxp3Frontiers in immunology · 2024Review
- Moderate regular physical exercise can help in alleviating the systemic impact of schistosomiasis infection on brain cognitive function.Frontiers in immunology · 2024Article
- Cysteinyl leukotriene receptor-1 as a potential target for host-directed therapy during chronic schistosomiasis in murine model.Frontiers in immunology · 2024Article
- The divergent outcome of IL-4Rα signalling on Foxp3 T regulatory cells in listeriosis and tuberculosis.Frontiers in immunology · 2024Article
- Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation.NPJ biofilms and microbiomes · 2023Article
- Differences in allergen-specific basophil activation and T cell proliferation in atopic dermatitis patients with comorbid allergic rhinoconjunctivitis treated with a monoclonal anti-IL-4Rα antibody or allergen-specific immunotherapy.Immunity, inflammation and disease · 2023Article
- IL-4Rα signalling in B cells and T cells play differential roles in acute and chronic atopic dermatitis.Scientific reports · 2023Article
- Schistosoma mansoni infection induces plasmablast and plasma cell death in the bone marrow and accelerates the decline of host vaccine responses.PLoS pathogens · 2022Article
- The Mechanisms of Effector Th Cell Responses Contribute to Treg Cell Function: New Insights into Pathogenesis and Therapy of Asthma.Frontiers in immunology · 2022Review
- The Road to Elimination: Current State of Schistosomiasis Research and Progress Towards the End Game.Frontiers in immunology · 2022Review
- Schistosome immunomodulators.PLoS pathogens · 2021Review
- Transgenic expression of a T cell epitope in Strongyloides ratti reveals that helminth-specific CD4+ T cells constitute both Th2 and Treg populations.PLoS pathogens · 2021Article
- Article
- Article
- IL-4Rα signaling in CD4+CD25+FoxP3+ T regulatory cells restrains airway inflammation via limiting local tissue IL-33.JCI insight · 2020Article
- Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities.PLoS pathogens · 2020Review
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Authors and funding
4 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Forkhead box P3 (Foxp3+) regulatory T (Treg)-cell function is controlled by environmental cues of which cytokine-mediated signaling is a dominant component. In vivo, interleukin-4 (IL-4)-mediated signaling via IL-4 receptor alpha (IL-4Rα) mediates Treg cell transdifferentiation into ex-Foxp3 T helper 2 (Th2) or T helper 17 (Th17) cells. However, IL-4-mediated signaling also reinforces the Foxp3 Treg compartment in vitro. We generated Foxp3-specific IL-4Rα-deficient mice and demonstrated differential efficiency of IL-4Rα deletion in male (approximately 90%) and female (approximately 40%) animals, because of cyclic recombinase (Cre)-mediated X-linked foxp3 inactivation. Irrespective of the degree of IL-4Rα deletion within the Foxp3+ Treg cell population, mice showed exacerbation of immune effector responses with aggravated tissue pathology in tissue-dwelling helminth infections (Schistosoma mansoni or Nippostrongylus brasiliensis). Mechanistically, IL-4Rα deletion in males and females led to a reduced expression of Foxp3 and subsequently an impaired accumulation of Foxp3+ Treg cells to inflamed tissues. In-depth cellular typing by flow cytometry revealed that the impairment of IL-4Rα-mediated signaling during helminth infections decreased the ability of central Treg cells to convert into effector Treg (eTreg) cells and caused a significant down-regulation of markers associated with Treg cell migration (C-X-C motif chemokine receptor 3 [CXCR3]) and accumulation in inflamed tissues (GATA binding protein 3 [GATA3]) as well as survival (B cell lymphoma 2 [Bcl-2]). These findings unprecedentedly, to our knowledge, uncover a role for IL-4Rα signaling in the positive regulation of Foxp3+ Treg cell function in vivo. Complementing our past knowledge on a widely reported role for IL-4Rα signaling in the negative regulation and transdifferentiation of Foxp3+ Treg cells in vivo, our present findings reveal the host requirement for an intact, but not reduced or potentiated, IL-4Rα-mediated signaling on Foxp3+ Treg cells to optimally control inflammation during helminth infections.
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