NDLI: GM-CSF but not IL-17 is critical for the development of severe interstitial lung disease in SKG mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mimori, Tsuneyo Shimizu, Masakazu Usui, Takashi Ishikawa, Yuki Murakami, Kosaku Shiomi, Aoi
Description	Country affiliation: Japan Author Affiliation: Shiomi A ( Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.); Usui T ( Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan takausui@kuhp.kyoto-u.ac.jp.); Ishikawa Y ( Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.); Shimizu M ( Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.); Murakami K ( Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.); Mimori T ( Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.)
Abstract	Interstitial lung disease (ILD) is a common complication and sometimes a prognostic factor of connective tissue diseases (CTDs) in humans. However, suitable animal model of severe CTD-associated ILD (CTD-ILD) has been limited. In this study, we showed that zymosan-treated SKG mice developed not only arthritis but also chronic-progressive ILD with high mortality over several months. The pathological and clinical features of ILD in zymosan-treated SKG mice were similar to that of human severe CTD-ILD. ILD in this mouse was characterized by massive infiltration of Th17 cells, GM-CSF-producing CD4(+) T cells, and CD11b(+) Gr1(+) neutrophils with fibrosis. Naive SKG T cells were skewed to differentiate into GM-CSF-producing cells, and GM-CSF secreted by T cells enhanced IL-6 and IL-1ß production by macrophages, which in turn enhanced differentiation of IL-17A- and/or GM-CSF-producing T cells and infiltration of neutrophils into lung. Neutralization of GM-CSF completely blocked the development of this ILD, and the blocking of IL-6 signaling resulted in partial prevention of it, whereas neutralization of IL-17A did not. In contrast, the progression of arthritis was inhibited by the neutralization of GM-CSF and slightly by the neutralization of IL-17A, but not by the blocking of IL-6 signaling. These data suggested zymosan-treated SKG mice could be a useful mouse model of severe CTD-ILD, and GM-CSF, rather than IL-17A or IL-6, contributed to the development of ILD in zymosan-treated SKG mice, indicating that neutralization of GM-CSF would be a useful therapeutic strategy for severe CTD-ILD.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	2
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-07-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Arthritis Immunology Granulocyte-macrophage Colony-stimulating Factor Interleukin-17 Lung Diseases, Interstitial Animals Antibodies, Neutralizing Pharmacology Chemically Induced Prevention & Control Cd4-positive T-lymphocytes Metabolism Cells, Cultured Connective Tissue Diseases Pathology Disease Models, Animal Flow Cytometry Antagonists & Inhibitors Interleukin-1beta Interleukin-6 Lung Drug Effects Macrophages Mice Mice, Inbred Balb C Neutrophils Severity Of Illness Index Th17 Cells Time Factors Zymosan Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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