Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice
BackgroundRecent in vitro studies strongly implicated mast cell-derived proteases as regulators of IL-33 activity by enzymatic cleavage in its central domain. A better understanding of the role of mast cell proteases on IL-33 activity in vivo is needed. We aimed to compare the expression of mast cel...
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| Format: | Article |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1040493/full |
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| author | Olga Krysko Darya Korsakova Andrea Teufelberger Andrea Teufelberger Amse De Meyer Jill Steels Natalie De Ruyck Judith van Ovost Sharon Van Nevel Gabriele Holtappels Frauke Coppieters Mikhail Ivanchenko Harald Braun Harald Braun Maria Vedunova Dmitri V. Krysko Dmitri V. Krysko Claus Bachert Claus Bachert Claus Bachert |
| author_facet | Olga Krysko Darya Korsakova Andrea Teufelberger Andrea Teufelberger Amse De Meyer Jill Steels Natalie De Ruyck Judith van Ovost Sharon Van Nevel Gabriele Holtappels Frauke Coppieters Mikhail Ivanchenko Harald Braun Harald Braun Maria Vedunova Dmitri V. Krysko Dmitri V. Krysko Claus Bachert Claus Bachert Claus Bachert |
| author_sort | Olga Krysko |
| collection | DOAJ |
| description | BackgroundRecent in vitro studies strongly implicated mast cell-derived proteases as regulators of IL-33 activity by enzymatic cleavage in its central domain. A better understanding of the role of mast cell proteases on IL-33 activity in vivo is needed. We aimed to compare the expression of mast cell proteases in C57BL/6 and BALB/c mice, their role in the cleavage of IL-33 cytokine, and their contribution to allergic airway inflammation.ResultsIn vitro, full-length IL-33 protein was efficiently degraded by mast cell supernatants of BALB/c mice in contrast to the mast cell supernatants from C57BL/6 mice. RNAseq analysis indicated major differences in the gene expression profiles of bone marrow-derived mast cells from C57BL/6 and BALB/c mice. In Alternaria alternata (Alt) - treated C57BL/6 mice the full-length form of IL-33 was mainly present, while in BALB/c mice, the processed shorter form of IL-33 was more prominent. The observed cleavage pattern of IL-33 was associated with a nearly complete lack of mast cells and their proteases in the lungs of C57BL/6 mice. While most inflammatory cells were similarly increased in Alt-treated C57BL/6 and BALB/c mice, C57BL/6 mice had significantly more eosinophils in the bronchoalveolar lavage fluid and IL-5 protein levels in their lungs than BALB/c mice.ConclusionOur study demonstrates that lung mast cells differ in number and protease content between the two tested mouse strains and could affect the processing of IL-33 and inflammatory outcome of Alt -induced airway inflammation. We suggest that mast cells and their proteases play a regulatory role in IL-33-induced lung inflammation by limiting its proinflammatory effect via the IL-33/ST2 signaling pathway. |
| first_indexed | 2024-04-09T17:19:25Z |
| format | Article |
| id | doaj.art-6dd9876d8f9f45ccb13d05891dad68e4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T17:19:25Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-6dd9876d8f9f45ccb13d05891dad68e42023-04-19T04:47:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.10404931040493Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in miceOlga Krysko0Darya Korsakova1Andrea Teufelberger2Andrea Teufelberger3Amse De Meyer4Jill Steels5Natalie De Ruyck6Judith van Ovost7Sharon Van Nevel8Gabriele Holtappels9Frauke Coppieters10Mikhail Ivanchenko11Harald Braun12Harald Braun13Maria Vedunova14Dmitri V. Krysko15Dmitri V. Krysko16Claus Bachert17Claus Bachert18Claus Bachert19Upper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, BelgiumInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, RussiaUpper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, BelgiumDepartment of Dermatology and Venereology, Medical University of Graz, Graz, AustriaUpper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, BelgiumUpper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, BelgiumUpper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, BelgiumUpper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, BelgiumUpper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, BelgiumUpper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, BelgiumCenter for Medical Genetics Ghent (CMGG), Department of Biomolecular Medicine, Ghent University, Ghent, BelgiumInstitute of Information Technology, Mathematics and Mechanics, National Research Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, RussiaUnit for Structural Biology, VIB-UGent Center for Inflammation Research, Ghent University, Ghent, BelgiumUnit for Structural Biology, Department of Biochemistry and Microbiology, Ghent University, Ghent, BelgiumInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, RussiaCell Death Investigation and Therapy Laboratory, Department of Human Structure and Repair, Ghent University, Ghent, BelgiumDepartment of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University), Moscow, RussiaUpper Airways Research Laboratory, Department of Head and Skin, Ghent University, Ghent, Belgium0Department of Otorhinolaryngology - Head and Neck Surgery, University Hospital of Münster, Münster, Germany1First Affiliated Hospital, Sun Yat-Sen University, International Airway Research Center, Guangzhou, ChinaBackgroundRecent in vitro studies strongly implicated mast cell-derived proteases as regulators of IL-33 activity by enzymatic cleavage in its central domain. A better understanding of the role of mast cell proteases on IL-33 activity in vivo is needed. We aimed to compare the expression of mast cell proteases in C57BL/6 and BALB/c mice, their role in the cleavage of IL-33 cytokine, and their contribution to allergic airway inflammation.ResultsIn vitro, full-length IL-33 protein was efficiently degraded by mast cell supernatants of BALB/c mice in contrast to the mast cell supernatants from C57BL/6 mice. RNAseq analysis indicated major differences in the gene expression profiles of bone marrow-derived mast cells from C57BL/6 and BALB/c mice. In Alternaria alternata (Alt) - treated C57BL/6 mice the full-length form of IL-33 was mainly present, while in BALB/c mice, the processed shorter form of IL-33 was more prominent. The observed cleavage pattern of IL-33 was associated with a nearly complete lack of mast cells and their proteases in the lungs of C57BL/6 mice. While most inflammatory cells were similarly increased in Alt-treated C57BL/6 and BALB/c mice, C57BL/6 mice had significantly more eosinophils in the bronchoalveolar lavage fluid and IL-5 protein levels in their lungs than BALB/c mice.ConclusionOur study demonstrates that lung mast cells differ in number and protease content between the two tested mouse strains and could affect the processing of IL-33 and inflammatory outcome of Alt -induced airway inflammation. We suggest that mast cells and their proteases play a regulatory role in IL-33-induced lung inflammation by limiting its proinflammatory effect via the IL-33/ST2 signaling pathway.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1040493/fullIL-33mast cellsallergytype 2 inflammationprotease |
| spellingShingle | Olga Krysko Darya Korsakova Andrea Teufelberger Andrea Teufelberger Amse De Meyer Jill Steels Natalie De Ruyck Judith van Ovost Sharon Van Nevel Gabriele Holtappels Frauke Coppieters Mikhail Ivanchenko Harald Braun Harald Braun Maria Vedunova Dmitri V. Krysko Dmitri V. Krysko Claus Bachert Claus Bachert Claus Bachert Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice Frontiers in Immunology IL-33 mast cells allergy type 2 inflammation protease |
| title | Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice |
| title_full | Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice |
| title_fullStr | Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice |
| title_full_unstemmed | Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice |
| title_short | Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice |
| title_sort | differential protease content of mast cells and the processing of il 33 in alternaria alternata induced allergic airway inflammation in mice |
| topic | IL-33 mast cells allergy type 2 inflammation protease |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1040493/full |
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