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Deciphering the therapeutic potential of Myeloid-Specific JAK2 inhibition in acute respiratory distress syndrome.
Gao, Shupei; Li, Wenjuan; Huang, Zhiwen; Deiuliis, Jeffrey A; Braunstein, Zachary; Liu, Xinxin; Li, Xinlu; Kosari, Mohammadreza; Chen, Jun; Min, Xinwen; Yang, Handong; Gong, Quan; Liu, Zheng; Wei, Yingying; Zhang, Ziyang; Dong, Lingli; Zhong, Jixin.
Afiliación
  • Gao S; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • Li W; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • Huang Z; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • Deiuliis JA; Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Braunstein Z; Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
  • Liu X; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • Li X; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • Kosari M; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • Chen J; Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, Hubei 442008, China.
  • Min X; Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, Hubei 442008, China.
  • Yang H; Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, Hubei 442008, China.
  • Gong Q; Department of Immunology, School of Medicine, Yangtze University, Jingzhou, Hubei 434023, China.
  • Liu Z; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Wei Y; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • Zhang Z; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan 430030, China.
  • Dong L; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: tjhdongll@163.com.
  • Zhong J; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH 44106, USA; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji M
Mucosal Immunol ; 2024 Aug 21.
Article en En | MEDLINE | ID: mdl-39173745
ABSTRACT
Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by severe inflammation and pulmonary dysfunction. Despite advancements in critical care, effective pharmacological interventions for ARDS remain elusive. While Janus kinase 2 (JAK2) inhibitors have emerged as an innovative treatment for numerous autoinflammatory diseases, their therapeutic potential in ARDS remains unexplored. In this study, we investigated the contribution of JAK2 and its underlying mechanisms in ARDS utilizing myeloid-specific JAK2 knockout murine models alongside a pharmacological JAK2 inhibitor. Notably, myeloid-specific JAK2 knockout led to a notable attenuation of ARDS induced by intratracheal administration of LPS, accompanied by reduced levels of neutrophils and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissue. Intriguingly, the ameliorative effects were abolished upon the depletion of monocyte-derived alveolar macrophages (Mo-AMs) rather than tissue-resident alveolar macrophages (TR-AMs). JAK2 deficiency markedly reversed LPS-induced activation of STAT5 in macrophages. Remarkably, pharmacological JAK2 inhibition using baricitinib failed to substantially alleviate neutrophils infiltration, implying that specific inhibition of JAK2 in Mo-AMs is imperative for ARDS amelioration. Collectively, our data suggest that JAK2 may mitigate ARDS progression through the JAK2 pathway in Mo-AMs, underscoring JAK2 in alveolar macrophages, particularly Mo-AMs, as a promising therapeutic target for ARDS treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos