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Evaluation of Lung Lesions in LATY136F Mutant Mice
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A3020 - Evaluation of Lung Lesions in LATY136F Mutant Mice
Author Block: Y. Waseda1, S. Matsui2, K. Yamada3, K. Mizuguchi4, S. Watanabe5, K. Ito3, M. Zuka3, M. Malissen6, B. Malissen6, M. Kawano3, T. Ishizuka1; 1Respiratory medicine, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Japan, 2Dept of 1st Internal Medicine, University of Toyama, Toyama-shi, Toyama, Japan, 3Kanazawa University, Kanazawa, Japan, 4JCHO Kanazawa Hospital, Kanazawa, Japan, 5Respiratory Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan, 6Aix‐Marseille University, Aix-en-Provence, France.
[Background] IgG4 related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4 positive plasma cells. A pathological change is famous for the pancreas, lacrimal gland and salivary glands, and lung pathological change also exists. LAT Y136F Knock-in mice (Lat mice) show Th2 predominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4. In ERS2014, we estimated lung lesion of Lat mice and concluded they would constitute an appropriate model of lung lesion for human IgG4-RD.
[Objective] The aim of this study is to estimate inflammation and fibrosis of lung lesion of Lat mice additionally.
[Methods] Lat mice (Homo) and wild-type mice (WT) were included in this study. Lung tissue samples were performed immunostaining of IgG1 and were obtained for pathological evaluation, and cell fractions and cytokine levels of broncho-alveolar lavage fleid (BALF) were analyzed.
[Results] In LAT group, IgG1 positive inflammatory cells increased from 4 weeks and achieved a peak at 10 weeks. In analysis of BALF, total cell count and percentage of lymphocyte increased significantly in Homo group than in WT group. In BALF, Th2 dominant cytokines and TGF-beta was also increased.
In LAT group, marked inflammation around broncho-vascular bandles achieved a peak at 10 weeks. And after 10 weeks, fibrosis around broncho-vascular bandles and bronchiectasis were observed, but not in WT group.
[Conclusion] In LAT group, IgG1 positive inflammatory cell was infiltrated in the early stage, and fibrosis was increased in the end stage.
Author Block: Y. Waseda1, S. Matsui2, K. Yamada3, K. Mizuguchi4, S. Watanabe5, K. Ito3, M. Zuka3, M. Malissen6, B. Malissen6, M. Kawano3, T. Ishizuka1; 1Respiratory medicine, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Japan, 2Dept of 1st Internal Medicine, University of Toyama, Toyama-shi, Toyama, Japan, 3Kanazawa University, Kanazawa, Japan, 4JCHO Kanazawa Hospital, Kanazawa, Japan, 5Respiratory Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan, 6Aix‐Marseille University, Aix-en-Provence, France.
[Background] IgG4 related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4 positive plasma cells. A pathological change is famous for the pancreas, lacrimal gland and salivary glands, and lung pathological change also exists. LAT Y136F Knock-in mice (Lat mice) show Th2 predominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4. In ERS2014, we estimated lung lesion of Lat mice and concluded they would constitute an appropriate model of lung lesion for human IgG4-RD.
[Objective] The aim of this study is to estimate inflammation and fibrosis of lung lesion of Lat mice additionally.
[Methods] Lat mice (Homo) and wild-type mice (WT) were included in this study. Lung tissue samples were performed immunostaining of IgG1 and were obtained for pathological evaluation, and cell fractions and cytokine levels of broncho-alveolar lavage fleid (BALF) were analyzed.
[Results] In LAT group, IgG1 positive inflammatory cells increased from 4 weeks and achieved a peak at 10 weeks. In analysis of BALF, total cell count and percentage of lymphocyte increased significantly in Homo group than in WT group. In BALF, Th2 dominant cytokines and TGF-beta was also increased.
In LAT group, marked inflammation around broncho-vascular bandles achieved a peak at 10 weeks. And after 10 weeks, fibrosis around broncho-vascular bandles and bronchiectasis were observed, but not in WT group.
[Conclusion] In LAT group, IgG1 positive inflammatory cell was infiltrated in the early stage, and fibrosis was increased in the end stage.
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