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

Stutz, Regine and Meyer, Christopher and Kaiser, Elisabeth and Goedicke-Fritz, Sybelle and Schroeder, Harry W. and Bals, Robert and Haertel, Christoph and Rogosch, Tobias and Kerzel, Sebastian and Zemlin, Michael (2021) Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire. SCIENTIFIC REPORTS, 11 (1): 14199. ISSN 2045-2322,

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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 T(H)2 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.

Item Type: Article
Uncontrolled Keywords: TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; INNATE LYMPHOID-CELLS; T-CELLS; B-CELL; AIRWAY INFLAMMATION; IGE TRANSCRIPTS; TYPE-2 IMMUNITY; MURINE MODEL; D-H; MECHANISMS;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Kinder- und Jugendmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 20 Sep 2022 13:10
Last Modified: 20 Sep 2022 13:10
URI: https://pred.uni-regensburg.de/id/eprint/47634

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