Evaluation of lung lesions in LATY136F mutant mice ∼Are they recognized as the models of IgG4 related lung disease?∼

[Background] The transmembrane protein LAT, linker for activation of T cells, couples the T cell receptor to downstream signaling effectors. LAT Y136F Knock-in mice (Lat mice) harbor a point mutation in Tyr136 of the linker for activation of T cells and show Th2 predominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4. 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. [Objective] The aim of this study is to estimate lung lesion of Lat mice and evaluate whether Lat mice would constitute an appropriate model of lung lesion for human IgG4-RD. [Methods]Lat mice (Homo) and wild-type mice (WT) were included in this study. Lung tissue samples were obtained for pathological evaluation, and cell fractions of broncho-alveolar lavage fleud (BALF) were analyzed. [Results] Marked inflammation and fibrosis of lung were observed in Homo group, but not in WT group. Lymphocytic infiltration and IgG1 positive plasma cells were seen around broncho-vascular bundles. In analysis of BALF, total cell count and percentage of lymphocyte increased significantly in Homo group than in WT group. (4.4±8.4*10 5 /μl (p l 0.005), 62.0±30.7% (p l 0.005)) [Conclusion] The features of lung lesion of Lat mice have a similar with those of human IgG4-RD. We considered that Lat mice are useful as a model for IgG4-RD.