The Foxp3+ regulatory T-cell population requires IL-4R$α$ signaling to control inflammation during helminth infections. Abdel Aziz, N., Nono, J. K., Mpotje, T., & Brombacher, F. PLOS Biology, 16(10):e2005850, oct, 2018. ![The Foxp3+ regulatory T-cell population requires IL-4R$α$ signaling to control inflammation during helminth infections [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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-4R$α$) 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-4R$α$-deficient mice and demonstrated differential efficiency of IL-4R$α$ 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-4R$α$ 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-4R$α$ 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-4R$α$-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-4R$α$ signaling in the positive regulation of Foxp3+ Treg cell function in vivo. Complementing our past knowledge on a widely reported role for IL-4R$α$ 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-4R$α$-mediated signaling on Foxp3+ Treg cells to optimally control inflammation during helminth infections.
@article{AbdelAziz2018,
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-4R$\alpha$) 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-4R$\alpha$-deficient mice and demonstrated differential efficiency of IL-4R$\alpha$ 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-4R$\alpha$ 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-4R$\alpha$ 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-4R$\alpha$-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-4R$\alpha$ signaling in the positive regulation of Foxp3+ Treg cell function in vivo. Complementing our past knowledge on a widely reported role for IL-4R$\alpha$ 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-4R$\alpha$-mediated signaling on Foxp3+ Treg cells to optimally control inflammation during helminth infections.},
author = {{Abdel Aziz}, Nada and Nono, Justin Komguep and Mpotje, Thabo and Brombacher, Frank},
doi = {10.1371/journal.pbio.2005850},
editor = {Marrack, Philippa},
issn = {1545-7885},
journal = {PLOS Biology},
keywords = {OA,fund{\_}not{\_}ack,original},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {oct},
number = {10},
pages = {e2005850},
pmid = {30379806},
title = {{The Foxp3+ regulatory T-cell population requires IL-4R$\alpha$ signaling to control inflammation during helminth infections}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/30379806 http://dx.plos.org/10.1371/journal.pbio.2005850 https://dx.plos.org/10.1371/journal.pbio.2005850},
volume = {16},
year = {2018}
}
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Irrespective of the degree of IL-4R$α$ 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-4R$α$ 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-4R$α$-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-4R$α$ signaling in the positive regulation of Foxp3+ Treg cell function in vivo. Complementing our past knowledge on a widely reported role for IL-4R$α$ 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-4R$α$-mediated signaling on Foxp3+ Treg cells to optimally control inflammation during helminth infections.","author":[{"propositions":[],"lastnames":["Abdel Aziz"],"firstnames":["Nada"],"suffixes":[]},{"propositions":[],"lastnames":["Nono"],"firstnames":["Justin","Komguep"],"suffixes":[]},{"propositions":[],"lastnames":["Mpotje"],"firstnames":["Thabo"],"suffixes":[]},{"propositions":[],"lastnames":["Brombacher"],"firstnames":["Frank"],"suffixes":[]}],"doi":"10.1371/journal.pbio.2005850","editor":[{"propositions":[],"lastnames":["Marrack"],"firstnames":["Philippa"],"suffixes":[]}],"issn":"1545-7885","journal":"PLOS Biology","keywords":"OA,fund_not_ack,original","mendeley-tags":"OA,fund_not_ack,original","month":"oct","number":"10","pages":"e2005850","pmid":"30379806","title":"The Foxp3+ regulatory T-cell population requires IL-4R$α$ signaling to control inflammation during helminth infections","url":"http://www.ncbi.nlm.nih.gov/pubmed/30379806 http://dx.plos.org/10.1371/journal.pbio.2005850 https://dx.plos.org/10.1371/journal.pbio.2005850","volume":"16","year":"2018","bibtex":"@article{AbdelAziz2018,\r\nabstract = {Forkhead box P3 (Foxp3+) regulatory T (Treg)-cell function is controlled by environmental cues of which cytokine-mediated signaling is a dominant component. 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