Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries
Abstract Type III interferons (λ1, λ2, and λ3) are potent antiviral cytokines in the lung. However, their roles in nonviral lung injuries are less well understood. This study investigates the activation of type III interferon signaling in three distinct models of lung injuries caused by diverse stim...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-10-01
|
| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.70104 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850201281581285376 |
|---|---|
| author | Jingjing Feng Jooyoung Kim Victoria D. Wang De Chang Hongbo Liu William G. Bain Keven M. Robinson Zhijun Jie Sergei V. Kotenko Charles S. Dela Cruz Lokesh Sharma |
| author_facet | Jingjing Feng Jooyoung Kim Victoria D. Wang De Chang Hongbo Liu William G. Bain Keven M. Robinson Zhijun Jie Sergei V. Kotenko Charles S. Dela Cruz Lokesh Sharma |
| author_sort | Jingjing Feng |
| collection | DOAJ |
| description | Abstract Type III interferons (λ1, λ2, and λ3) are potent antiviral cytokines in the lung. However, their roles in nonviral lung injuries are less well understood. This study investigates the activation of type III interferon signaling in three distinct models of lung injuries caused by diverse stimuli: the bacterial pathogen Pseudomonas aeruginosa, bacterial endotoxin LPS, and the chemotherapeutic agent bleomycin. Our data show that, despite inducing a potent inflammatory response, Pseudomonas and LPS did not increase IFNλ secretion. In contrast, bleomycin instillation increased secretion of IFNλ in the airways at both early and late time points. Consistent with limited secretion, type III interferon signaling had a minimal role in the host response to both Pseudomonas and LPS, as measured by pathogen burden, inflammatory response, and lung injury. Conversely, a deficiency in type III interferon signaling led to increased inflammatory signaling and elevated acute lung injury in the bleomycin model on day 3. This elevated early injury resulted in impaired recovery in IFNLR1 knockout mice, as evidenced by their recovery from bleomycin‐induced weight loss. Taken together, these data suggest a context‐specific activation of type III interferon signaling, where it plays an anti‐inflammatory role in the lung. |
| format | Article |
| id | doaj-art-f079971b4ef3452a86bee1efa3c2e971 |
| institution | OA Journals |
| issn | 2051-817X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-f079971b4ef3452a86bee1efa3c2e9712025-08-20T02:12:03ZengWileyPhysiological Reports2051-817X2024-10-011220n/an/a10.14814/phy2.70104Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuriesJingjing Feng0Jooyoung Kim1Victoria D. Wang2De Chang3Hongbo Liu4William G. Bain5Keven M. Robinson6Zhijun Jie7Sergei V. Kotenko8Charles S. Dela Cruz9Lokesh Sharma10Department of Pulmonary and Critical Care Medicine, Shanghai Fifth People's Hospital, Center of Community‐Based Health Research Fudan University Shanghai ChinaSection of Pulmonary, Critical Care and Sleep Medicine Yale School of Medicine New Haven Connecticut USADivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USASection of Pulmonary, Critical Care and Sleep Medicine Yale School of Medicine New Haven Connecticut USASection of Pulmonary, Critical Care and Sleep Medicine Yale School of Medicine New Haven Connecticut USADivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USADivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USADepartment of Pulmonary and Critical Care Medicine, Shanghai Fifth People's Hospital, Center of Community‐Based Health Research Fudan University Shanghai ChinaDepartment of Biochemistry and Molecular Biology Rutgers New Jersey Medical School New Brunswick New Jersey USASection of Pulmonary, Critical Care and Sleep Medicine Yale School of Medicine New Haven Connecticut USASection of Pulmonary, Critical Care and Sleep Medicine Yale School of Medicine New Haven Connecticut USAAbstract Type III interferons (λ1, λ2, and λ3) are potent antiviral cytokines in the lung. However, their roles in nonviral lung injuries are less well understood. This study investigates the activation of type III interferon signaling in three distinct models of lung injuries caused by diverse stimuli: the bacterial pathogen Pseudomonas aeruginosa, bacterial endotoxin LPS, and the chemotherapeutic agent bleomycin. Our data show that, despite inducing a potent inflammatory response, Pseudomonas and LPS did not increase IFNλ secretion. In contrast, bleomycin instillation increased secretion of IFNλ in the airways at both early and late time points. Consistent with limited secretion, type III interferon signaling had a minimal role in the host response to both Pseudomonas and LPS, as measured by pathogen burden, inflammatory response, and lung injury. Conversely, a deficiency in type III interferon signaling led to increased inflammatory signaling and elevated acute lung injury in the bleomycin model on day 3. This elevated early injury resulted in impaired recovery in IFNLR1 knockout mice, as evidenced by their recovery from bleomycin‐induced weight loss. Taken together, these data suggest a context‐specific activation of type III interferon signaling, where it plays an anti‐inflammatory role in the lung.https://doi.org/10.14814/phy2.70104bleomycinfibrosislung inflammationlung injurytype III interferons |
| spellingShingle | Jingjing Feng Jooyoung Kim Victoria D. Wang De Chang Hongbo Liu William G. Bain Keven M. Robinson Zhijun Jie Sergei V. Kotenko Charles S. Dela Cruz Lokesh Sharma Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries Physiological Reports bleomycin fibrosis lung inflammation lung injury type III interferons |
| title | Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries |
| title_full | Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries |
| title_fullStr | Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries |
| title_full_unstemmed | Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries |
| title_short | Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries |
| title_sort | context specific anti inflammatory roles of type iii interferon signaling in the lung in nonviral injuries |
| topic | bleomycin fibrosis lung inflammation lung injury type III interferons |
| url | https://doi.org/10.14814/phy2.70104 |
| work_keys_str_mv | AT jingjingfeng contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT jooyoungkim contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT victoriadwang contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT dechang contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT hongboliu contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT williamgbain contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT kevenmrobinson contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT zhijunjie contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT sergeivkotenko contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT charlessdelacruz contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries AT lokeshsharma contextspecificantiinflammatoryrolesoftypeiiiinterferonsignalinginthelunginnonviralinjuries |