Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire

Abstract We hypothesized that the scarcity of N-nucleotides might contribute to the inability of the neonate to mount a robust allergic immune response. To test this, we used terminal deoxyribunucleotidyl Transferase deficient (TdT−/−) mice, which express “fetal-like” T cell receptor and immunoglobu...

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Autores principales:	Regine Stutz, Christopher Meyer, Elisabeth Kaiser, Sybelle Goedicke-Fritz, Harry W. Schroeder, Robert Bals, Christoph Haertel, Tobias Rogosch, Sebastian Kerzel, Michael Zemlin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b8e090760254a5383816ea9541a8604
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spelling	oai:doaj.org-article:5b8e090760254a5383816ea9541a86042021-12-02T16:15:06ZAttenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire10.1038/s41598-021-93553-62045-2322https://doaj.org/article/5b8e090760254a5383816ea9541a86042021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93553-6https://doaj.org/toc/2045-2322Abstract We hypothesized that the scarcity of N-nucleotides might contribute to the inability of the neonate to mount a robust allergic immune response. To test this, we used terminal deoxyribunucleotidyl Transferase deficient (TdT−/−) mice, which express “fetal-like” T cell receptor and immunoglobulin repertoires with largely germline-encoded CDR3 regions. Intraperitoneal sensitization was followed by aerosol provocation with either PBS or the allergen OVA in both TdT−/− mice and wild-type mice to develop allergic respiratory inflammation. The effects of this procedure were investigated by lung function test, immunological analysis of serum and brochoalveolar lavage. The local TH2 cytokine milieu was significantly attenuated in TdT−/− mice. Within this group, the induction of total IgE levels was also significantly reduced after sensitization. TdT−/− mice showed a tendency toward reduced eosinophilic inflow into the bronchial tubes, which was associated with the elimination of respiratory hyperreactivity. In conclusion, in a murine model of allergic airway inflammation, the expression of fetal-like antigen receptors was associated with potent indications of a reduced ability to mount an asthma phenotype. This underlines the importance of somatically-generated antigen-receptor repertoire diversity in type one allergic immune responses and suggests that the fetus may be protected from allergic responses, at least in part, by controlling N addition.Regine StutzChristopher MeyerElisabeth KaiserSybelle Goedicke-FritzHarry W. SchroederRobert BalsChristoph HaertelTobias RogoschSebastian KerzelMichael ZemlinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Regine Stutz Christopher Meyer Elisabeth Kaiser Sybelle Goedicke-Fritz Harry W. Schroeder Robert Bals Christoph Haertel Tobias Rogosch Sebastian Kerzel Michael Zemlin Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire
description	Abstract We hypothesized that the scarcity of N-nucleotides might contribute to the inability of the neonate to mount a robust allergic immune response. To test this, we used terminal deoxyribunucleotidyl Transferase deficient (TdT−/−) mice, which express “fetal-like” T cell receptor and immunoglobulin repertoires with largely germline-encoded CDR3 regions. Intraperitoneal sensitization was followed by aerosol provocation with either PBS or the allergen OVA in both TdT−/− mice and wild-type mice to develop allergic respiratory inflammation. The effects of this procedure were investigated by lung function test, immunological analysis of serum and brochoalveolar lavage. The local TH2 cytokine milieu was significantly attenuated in TdT−/− mice. Within this group, the induction of total IgE levels was also significantly reduced after sensitization. TdT−/− mice showed a tendency toward reduced eosinophilic inflow into the bronchial tubes, which was associated with the elimination of respiratory hyperreactivity. In conclusion, in a murine model of allergic airway inflammation, the expression of fetal-like antigen receptors was associated with potent indications of a reduced ability to mount an asthma phenotype. This underlines the importance of somatically-generated antigen-receptor repertoire diversity in type one allergic immune responses and suggests that the fetus may be protected from allergic responses, at least in part, by controlling N addition.
format	article
author	Regine Stutz Christopher Meyer Elisabeth Kaiser Sybelle Goedicke-Fritz Harry W. Schroeder Robert Bals Christoph Haertel Tobias Rogosch Sebastian Kerzel Michael Zemlin
author_facet	Regine Stutz Christopher Meyer Elisabeth Kaiser Sybelle Goedicke-Fritz Harry W. Schroeder Robert Bals Christoph Haertel Tobias Rogosch Sebastian Kerzel Michael Zemlin
author_sort	Regine Stutz
title	Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire
title_short	Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire
title_full	Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire
title_fullStr	Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire
title_full_unstemmed	Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire
title_sort	attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5b8e090760254a5383816ea9541a8604
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Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire

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