PDGFRα-positive cell-derived TIMP-1 modulates adaptive immune responses to influenza A viral infection

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 328; no. 1; pp. L60 - L74
• Main Authors: Dutta, Saugata, Zhu, Yin, Almuntashiri, Sultan, Peh, Hong Yong, Zuñiga, Joaquin, Zhang, Duo, Somanath, Payaningal R., Ramírez, Gustavo, Irineo-Moreno, Valeria, Jiménez-Juárez, Fabiola, López-Salinas, Karen, Regino, Nora, Campero, Paloma, Crocker, Stephen J., Owen, Caroline A., Wang, Xiaoyun
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2025
• Subjects: Adaptive Immunity; Animals; Bronchus; Clonal deletion; CXCL12 protein; Female; Growth factors; Humans; Immune response; In vivo methods and tests; Infections; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - immunology; Influenza, Human - immunology; Lavage; Leukocytes (neutrophilic); Lung - immunology; Lung - metabolism; Lung - pathology; Lung - virology; Lungs; Lymphocytes; Lymphocytes T; Macrophages; Male; Matrix metalloproteinase; Matrix metalloproteinases; Mice; Mice, Inbred C57BL; Mice, Knockout; Mortality; Myofibroblasts - immunology; Myofibroblasts - metabolism; Myofibroblasts - pathology; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; Pathogenesis; Physiology; Plasma levels; Receptor, Platelet-Derived Growth Factor alpha - genetics; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Therapeutic targets; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Weight loss; lipofibroblast; PDGFRα; CXCL12; myofibroblast; adaptive immunity

Our data strongly link tissue inhibitor of metalloproteinases-1 (TIMP-1) to influenza A virus (IAV) pathogenesis. TIMP-1 is highly increased in PDGFRα-lineage cells during IAV infection. Transforming growth factor-β (TGF-β) induces TIMP-1 during lipofibroblast (lipoFB)-to- myofibroblast (myoFB) tran...