The immunopathology of lung fibrosis: amphiregulin-producing pathogenic memory T helper-2 cells control the airway fibrotic responses by inducing eosinophils to secrete osteopontin

• Published in: Seminars in immunopathology 2019-05, Vol.41 (3), p.339-348
• Main Authors: Hirahara, Kiyoshi, Aoki, Ami, Morimoto, Yuki, Kiuchi, Masahiro, Okano, Mikiko, Nakayama, Toshinori
• Format: Article
• Language: English
• Subjects: Amphiregulin; Amphiregulin - biosynthesis; Animals; Asthma; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cytokines - metabolism; Disease Models, Animal; Disease Susceptibility - immunology; Disease Susceptibility - metabolism; Eosinophils - immunology; Eosinophils - metabolism; Eosinophils - pathology; Extracellular matrix; Fibrosis; Helper cells; Humans; Immunologic Memory; Immunological memory; Immunology; Inflammatory diseases; Internal Medicine; Leukocytes (eosinophilic); Lung diseases; Lymphocytes T; Mice; Molecular modelling; Osteopontin; Osteopontin - metabolism; Parenchyma; Pulmonary Fibrosis - etiology; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Respiratory Mucosa - pathology; Respiratory tract; Review; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 1863-2297; 1863-2300
• DOI: 10.1007/s00281-019-00735-6

Fibrosis is defined as excessive deposition of the extracellular matrix (ECM) in the parenchyma of various organs, and sometimes leads to irreversible organ malfunction such as idiopathic pulmonary fibrosis (IPF), a fatal disorder of the lung. Chronic inflammatory stimuli induce fibrotic responses in various organs. Various immune cells, including T helper (Th) cells in the lung, protect the host from different harmful particles, including pathogenic microorganisms. However, the dysregulation of the function of these immune cells in the lung sometimes causes inflammatory diseases, such as lung fibrosis. In this review, we will introduce an outline of the cellular and molecular mechanisms underlying the pathogenic fibrotic responses in the lung. We will also introduce the concept of the “Pathogenic Th population disease induction model,” in which unique subpopulations of certain Th cell subsets control the pathology of immune-mediated inflammatory diseases. Finally, we introduce our recent findings, which demonstrate that amphiregulin-producing pathogenic memory Th2 cells control airway fibrosis through the osteopontin produced by inflammatory eosinophils. The identification of this new pathogenic Th cell population supports the concept of “Pathogenic Th population disease induction model”, and will provide novel strategies for treating intractable diseases, including lung fibrosis.