Sjogren's syndrome in the NOD mouse model is an interleukin-4 time-dependent, antibody isotype-specific autoimmune disease
Sjogren's syndrome in the NOD mouse model is an interleukin-4 time-dependent, antibody isotype-specific autoimmune disease
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DOI：
10.1016/j.jaut.2005.11.004
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发表时间：
2006-03-01
影响因子：
12.8
通讯作者：
Peck, AB
中科院分区：
文献类型：
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作者：
Gao, JH;Killedar, S;Peck, AB
点头。B10-H2(b)和NOD/LtJ小鼠分别表现出原发性和继发性干燥综合征（SjS）的许多特征，SjS是一种主要影响唾液腺和泪腺的自身免疫性疾病，可导致口干和干眼。先前的一项研究表明，T-H2细胞因子白细胞介素(IL)-4在NOD小鼠模型中sjs样疾病的发生和发展中起着不可或缺的作用。为了进一步确定IL-4在小鼠sjs样疾病发病中的作用，我们检测了两种IL-4基因敲除（KO）小鼠品系NOD。il - 4（-/-）和NOD.B10-H2(b). il - 4（-/-）。不像点头。il - 4（-/-）小鼠，NOD.B10-H2(b)。il - 4（-/-）小鼠对糖尿病的发展具有抗性。功能失调的IL4基因的存在并不妨碍白细胞浸润唾液腺，但阻止分泌功能障碍的发展。而NOD.B10-H2 (b)。IL4（-/-）小鼠表现出许多亲本菌株常见的sjs样疾病的病理生理表现，这些小鼠不能产生IgG1同型的抗musearinic乙酰胆碱3型受体（M3R）自身抗体。细胞因子mRNA表达谱和T淋巴细胞从NOD.B10-H2的过继转移(b)。Gfp小鼠注入NOD.B10-H2(b)。不同年龄的IL-4（-/-）小鼠表明在临床前疾病阶段（约12周龄）需要IL-4来启动临床口干症。本研究结果表明，NOD失效。il - 4（-/-）和NOD.B10-H2(b)。IL4（-/-）小鼠合成IgG1同型的抗m3r自身抗体，这显然解释了为什么这些小鼠尽管表现出sjs样疾病的临床前表现，但却没有发生外分泌腺功能障碍。(c) 2005 Elsevier Ltd版权所有。
NOD.B10-H2(b) and NOD/LtJ mice manifest many features of primary and secondary Sjogren's syndrome (SjS), respectively, an autoimmune disease affecting primarily the salivary and lacrimal glands leading to xerostomia (dry Mouth) and xerophthalmia (dry eyes). A previous study suggested that the T-H2 cytokine, interleukin (IL)-4, plays an integral role in the development and onset of SjS-like disease in the NOD Mouse model. To define further the role of IL-4 in onset of murine SjS-like disease, we have examined two IL4 gene knockout (KO) mouse strains, NOD.IL4(-/-) and NOD.B10-H2(b).IL4(-/-). Unlike NOD.IL4(-/-) mice, NOD.B10-H2(b).IL4(-/-) mice are resistant to development of diabetes. The presence of a dysfunctional IL4 gene did not impede leukocyte infiltration of the salivary glands, yet prevented development of secretory dysfunction. Whereas NOD.B10-H2(b).IL4(-/-) mice exhibited many pathophysiological manifestations of SjS-like disease common to the parental strains, these mice failed to produce anti-musearinic acetylcholine type-3 receptor (M3R) autoantibodies of the IgG1 isotype. Cytokine mRNA expression profiles and adoptive transfers of T lymphocytes from NOD.B10-H2(b).Gfp mice into NOD.B10-H2(b).IL4(-/-) mice at different ages suggest IL-4 is required during the pre-clinical disease stage (around 12 weeks of age) to initiate clinical xerostomia. The results of this study indicate that the failure of NOD.IL4(-/-) and NOD.B10-H2(b).IL4(-/-) mice to synthesize anti-M3R autoantibodies of the IgG1 isotype apparently explains why these mice fail to develop exocrine gland dysfunction, despite exhibiting pre-clinical manifestations of SjS-like disease. (c) 2005 Elsevier Ltd. All rights reserved.