In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 3 ( 2021-3-4), p. e0247173-
Abstract:
Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by an elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. Pathological changes are most frequently seen in the pancreas, lacrimal glands, and salivary glands, but pathological changes in the lung also exist. Linker for activation of T cell ( LAT ) Y136F knock-in mice show Th2-dominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4. We have reported that LAT Y136F knock-in mice display several characteristic features of IgG4-RD and concluded that they constitute an appropriate model of human IgG4-RD in salivary glands, pancreas, and kidney lesions. Objectives The aim of this study is to evaluate whether lung lesions in LAT Y136F knock-in mice can be a model of IgG4-related lung disease. Methods Lung tissue samples from LAT Y136F knock-in mice (LAT) and wild-type mice (WT) were immunostained for IgG1 and obtained for pathological evaluation, and cell fractions and cytokine levels in broncho-alveolar lavage fluid (BALF) were analyzed. Results In the LAT group, IgG1-positive inflammatory cells increased starting at 4 weeks of age and peaked at 10 weeks of age. The total cell count and percentage of lymphocytes increased significantly in BALF in the LAT group compared to the WT group. In BALF, Th2-dominant cytokines and transforming growth factor-β were also increased. In the LAT group, marked inflammation around broncho-vascular bundles peaked at 10 weeks of age. After 10 weeks, fibrosis around broncho-vascular bundles and bronchiectasis were observed in LAT Y136F knock-in mice but not WT mice. Conclusions LAT Y136F knock-in mice constitute an appropriate model of lung lesions in IgG4-RD.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0247173
DOI:
10.1371/journal.pone.0247173.g001
DOI:
10.1371/journal.pone.0247173.g002
DOI:
10.1371/journal.pone.0247173.g003
DOI:
10.1371/journal.pone.0247173.g004
DOI:
10.1371/journal.pone.0247173.g005
DOI:
10.1371/journal.pone.0247173.t001
DOI:
10.1371/journal.pone.0247173.s001
DOI:
10.1371/journal.pone.0247173.s002
DOI:
10.1371/journal.pone.0247173.r001
DOI:
10.1371/journal.pone.0247173.r002
DOI:
10.1371/journal.pone.0247173.r003
DOI:
10.1371/journal.pone.0247173.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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