Inception of early life allergen induced airway hyperresponsiveness is reliant on IL-13+CD4+ T cells
| Autor: | Avneet K. Manghera, William J. Branchett, Robert A. Oliver, Valentina Fainardi, Clare M. Lloyd, Laura Denney, Lewis J. Entwistle, Ruth Grychtol, Andrew Bush, Stephen Lui, Rebekah Sherburn, Lisa G. Gregory, Franz Puttur, Adam J. Byrne, Sejal Saglani, Simone A. Walker, Erika von Mutius, Jessica Vasiliou, David Vöhringer, Faith I. Uwadiae, James Buckley |
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| Přispěvatelé: | Wellcome Trust |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male CHILDHOOD CHILDREN Mice SCID medicine.disease_cause RESPONSIVENESS ACTIVATION 0302 clinical medicine Allergen Mice Knockout OUTCOMES Mice Inbred BALB C Interleukin-13 biology Acinetobacter Innate lymphoid cell Pyroglyphidae Alternaria General Medicine 3. Good health LUNG-FUNCTION Interleukin 13 Female Acinetobacter lwoffii Life Sciences & Biomedicine Immunology INNATE LYMPHOID-CELLS 03 medical and health sciences medicine Respiratory Hypersensitivity Animals Pulmonary Eosinophilia Asthma House dust mite TYPE-2 IMMUNITY Science & Technology business.industry Allergens medicine.disease biology.organism_classification Interleukin-33 respiratory tract diseases Interleukin 33 030104 developmental biology 030228 respiratory system Animals Newborn PEDIATRIC SEVERE ASTHMA business RESPONSES |
| Zdroj: | Sci. Immunol. 3:eaan4128 (2018) |
| Popis: | Airway hyperresponsiveness (AHR) is a critical feature of wheezing and asthma in children, but the initiating immune mechanisms remain unconfirmed. We demonstrate that both recombinant interleukin-33 (rIL-33) and allergen [ house dust mite (HDM) or Alternaria alternata] exposure from day 3 of life resulted in significantly increased pulmonary IL-13(+)CD4(+) T cells, which were indispensable for the development of AHR. In contrast, adult mice had a predominance of pulmonary Lin(neg)CD45(+)CD90(+)IL-13(+) type 2 innate lymphoid cells (ILC2s) after administration of rIL-33. HDM exposure of neonatal IL-33 knockout (KO) mice still resulted in AHR. However, neonatal CD4(cre)IL-13 KO mice (lacking IL-13(+)CD4(+) T cells) exposed to allergen from day 3 of life were protected from AHR despite persistent pulmonary eosinophilia, elevated IL-33 levels, and IL-13(+) ILCs. Moreover, neonatal mice were protected from AHR when inhaled Acinetobacter lwoffii (an environmental bacterial isolate found in cattle farms, which is known to protect from childhood asthma) was administered concurrent with HDM. A. lwoffii blocked the expansion of pulmonary IL-13(+)CD4(+) T cells, whereas IL-13(+) ILCs and IL-33 remained elevated. Administration of A. lwoffii mirrored the findings from the CD4(cre)IL-13 KO mice, providing a translational approach for disease protection in early life. These data demonstrate that IL-13(+)CD4(+) T cells, rather than IL-13(+) ILCs or IL-33, are critical for inception of allergic AHR in early life. |
| Databáze: | OpenAIRE |
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