Ki-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections
Abstract Neutrophils defend against respiratory infections but cause acute lung injury (ALI) when excessively recruited to the lung. Early life environmental factors can shape lung development, but how they impact neutrophil recruitment is not known. We show that exposing newborn mice to hyperoxia i...
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| Format: | Article |
| Language: | English |
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Springer Nature
2025-06-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1038/s44321-025-00261-z |
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| author | Min Yee Ravi Misra Sarah Vesecky Michael Barravecchia Rauf A Najar Arshad Rahman Gloria S Pryhuber David A Dean B Paige Lawrence Daniel Fisher Michael A O’Reilly |
| author_facet | Min Yee Ravi Misra Sarah Vesecky Michael Barravecchia Rauf A Najar Arshad Rahman Gloria S Pryhuber David A Dean B Paige Lawrence Daniel Fisher Michael A O’Reilly |
| author_sort | Min Yee |
| collection | DOAJ |
| description | Abstract Neutrophils defend against respiratory infections but cause acute lung injury (ALI) when excessively recruited to the lung. Early life environmental factors can shape lung development, but how they impact neutrophil recruitment is not known. We show that exposing newborn mice to hyperoxia increases the number of adult alveolar type 1 (AT1) epithelial cells expressing the proliferation marker Ki-67. Although these cells were not proliferating, they expressed high levels of chemokines that stimulated neutrophil recruitment and ALI when mice were infected with influenza A virus or exposed to lipopolysaccharide (LPS). Neutrophil recruitment and chemokine production were attenuated in Ki-67 hypomorph mice infected with virus or exposed to LPS and enhanced by genetically overexpressing Ki-67 in their lungs. Silencing Ki-67 in a mouse AT1-like cell line reduced basal and IL-1β stimulation of RelA/p65 and NF-κB-dependent transcription of the chemokines Cxcl1 and Cxcl5. Our findings reveal a novel role for Ki-67 to modulate the intensity of epithelial pro-inflammatory signaling, controlling neutrophil recruitment. The severity of respiratory infections may be influenced by mitogens and environmental factors that increase the expression of Ki-67. |
| format | Article |
| id | doaj-art-b581cacc9e0848dd89d841e7bb4c8d2b |
| institution | Kabale University |
| issn | 1757-4684 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-b581cacc9e0848dd89d841e7bb4c8d2b2025-08-20T03:42:52ZengSpringer NatureEMBO Molecular Medicine1757-46842025-06-011782011203910.1038/s44321-025-00261-zKi-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infectionsMin Yee0Ravi Misra1Sarah Vesecky2Michael Barravecchia3Rauf A Najar4Arshad Rahman5Gloria S Pryhuber6David A Dean7B Paige Lawrence8Daniel Fisher9Michael A O’Reilly10Division of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of RochesterDivision of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of RochesterDivision of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of RochesterDivision of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of RochesterDivision of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of RochesterDivision of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of RochesterDivision of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of RochesterDivision of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of RochesterDepartment of Environmental Medicine, School of Medicine & Dentistry, The University of RochesterInstitut de Génétique Moléculaire de Montpellier, CNRS, INSERM, Université de MontpellierDivision of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of RochesterAbstract Neutrophils defend against respiratory infections but cause acute lung injury (ALI) when excessively recruited to the lung. Early life environmental factors can shape lung development, but how they impact neutrophil recruitment is not known. We show that exposing newborn mice to hyperoxia increases the number of adult alveolar type 1 (AT1) epithelial cells expressing the proliferation marker Ki-67. Although these cells were not proliferating, they expressed high levels of chemokines that stimulated neutrophil recruitment and ALI when mice were infected with influenza A virus or exposed to lipopolysaccharide (LPS). Neutrophil recruitment and chemokine production were attenuated in Ki-67 hypomorph mice infected with virus or exposed to LPS and enhanced by genetically overexpressing Ki-67 in their lungs. Silencing Ki-67 in a mouse AT1-like cell line reduced basal and IL-1β stimulation of RelA/p65 and NF-κB-dependent transcription of the chemokines Cxcl1 and Cxcl5. Our findings reveal a novel role for Ki-67 to modulate the intensity of epithelial pro-inflammatory signaling, controlling neutrophil recruitment. The severity of respiratory infections may be influenced by mitogens and environmental factors that increase the expression of Ki-67.https://doi.org/10.1038/s44321-025-00261-zAcute Lung InjuryAlveolar Epithelial CellsInfluenza A VirusMiceSusceptibility |
| spellingShingle | Min Yee Ravi Misra Sarah Vesecky Michael Barravecchia Rauf A Najar Arshad Rahman Gloria S Pryhuber David A Dean B Paige Lawrence Daniel Fisher Michael A O’Reilly Ki-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections EMBO Molecular Medicine Acute Lung Injury Alveolar Epithelial Cells Influenza A Virus Mice Susceptibility |
| title | Ki-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections |
| title_full | Ki-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections |
| title_fullStr | Ki-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections |
| title_full_unstemmed | Ki-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections |
| title_short | Ki-67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections |
| title_sort | ki 67 promotes inflammatory signaling governing neutrophil recruitment during respiratory infections |
| topic | Acute Lung Injury Alveolar Epithelial Cells Influenza A Virus Mice Susceptibility |
| url | https://doi.org/10.1038/s44321-025-00261-z |
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