CD45 alleviates airway inflammation and lung fibrosis by limiting expansion and activation of ILC2s
Group 2 innate lymphoid cells (ILC2s) are critical for the immune response against parasite infection and tissue homeostasis and involved in the pathogenesis of allergy and inflammatory diseases. Although multiple molecules positively regulating ILC2 development and activation have been extensively investigated, the factors limiting their population size and response remain poorly studied. Here, we found that CD45, a membrane-bound tyrosine phosphatase essential for T cell development, negatively regulated ILC2s in a cell-intrinsic manner. ILC2s in CD45-deficient mice exhibited enhanced proliferation and maturation in the bone marrow and hyperactivated phenotypes in the lung with high glycolytic capacity. Furthermore, CD45 signaling suppressed the type 2 inflammatory response by lung ILC2s and alleviated airway inflammation and pulmonary fibrosis. Finally, the interaction with galectin-9 influenced CD45 signaling in ILC2s. These results demonstrate that CD45 is a cell-intrinsic negative regulator of ILC2s and prevents lung inflammation and fibrosis via ILC2s.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 120(2023), 36 vom: 05. Sept., Seite e2215941120 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cui, Guangwei [VerfasserIn] |
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| Links: |
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| Themen: |
Airway inflammation |
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| Anmerkungen: |
Date Completed 31.08.2023 Date Revised 29.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2215941120 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Group 2 innate lymphoid cells (ILC2s) are critical for the immune response against parasite infection and tissue homeostasis and involved in the pathogenesis of allergy and inflammatory diseases. Although multiple molecules positively regulating ILC2 development and activation have been extensively investigated, the factors limiting their population size and response remain poorly studied. Here, we found that CD45, a membrane-bound tyrosine phosphatase essential for T cell development, negatively regulated ILC2s in a cell-intrinsic manner. ILC2s in CD45-deficient mice exhibited enhanced proliferation and maturation in the bone marrow and hyperactivated phenotypes in the lung with high glycolytic capacity. Furthermore, CD45 signaling suppressed the type 2 inflammatory response by lung ILC2s and alleviated airway inflammation and pulmonary fibrosis. Finally, the interaction with galectin-9 influenced CD45 signaling in ILC2s. These results demonstrate that CD45 is a cell-intrinsic negative regulator of ILC2s and prevents lung inflammation and fibrosis via ILC2s | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a airway inflammation | |
| 650 | 4 | |a fibrosis | |
| 650 | 4 | |a innate lymphoid cell | |
| 650 | 4 | |a metabolism | |
| 700 | 1 | |a Shimba, Akihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Jianshi |e verfasserin |4 aut | |
| 700 | 1 | |a Hojo, Nozomi |e verfasserin |4 aut | |
| 700 | 1 | |a Asahi, Takuma |e verfasserin |4 aut | |
| 700 | 1 | |a Abe, Shinya |e verfasserin |4 aut | |
| 700 | 1 | |a Ejima, Aki |e verfasserin |4 aut | |
| 700 | 1 | |a Okada, Shinri |e verfasserin |4 aut | |
| 700 | 1 | |a Ohira, Keizo |e verfasserin |4 aut | |
| 700 | 1 | |a Kato, Ryoma |e verfasserin |4 aut | |
| 700 | 1 | |a Tani-Ichi, Shizue |e verfasserin |4 aut | |
| 700 | 1 | |a Yamada, Ryo |e verfasserin |4 aut | |
| 700 | 1 | |a Ebihara, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Shiroguchi, Katsuyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Ikuta, Koichi |e verfasserin |4 aut | |
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