Male gonadal environment paradoxically promotes dacryoadenitis in nonobese diabetic mice
Male gonadal environment paradoxically promotes dacryoadenitis in nonobese diabetic mice
复制标题
DOI：
10.1172/jci1230
复制
发表时间：
1998-03-15
影响因子：
15.9
通讯作者：
Mueller, C
中科院分区：
文献类型：
--
作者：
Hunger, RE;Carnaud, C;Mueller, C
与胰岛相似，雌性NOD小鼠的下颌下腺浸润速度比雄性更快。然而，对泪腺细胞浸润的比较分析显示了相反的结果。在12周龄时，大约25%的雄性泪腺组织区域被浸润，而年龄匹配的雌性NOD小鼠仍然缺乏炎症的主要体征。T细胞在浸润的早期占优势，但B细胞在更晚期迅速聚集，并最终超过T细胞。泪腺炎是由性激素促进的，如在切除卵巢的NOD男性中观察到的浸润减少所示（P < 0.01）。它也由泪腺组织提供的局部环境控制，来自4周龄和20周龄雌性NOD小鼠的脾细胞在过继转移到NOD雄性受体中时引起大面积病变，而相反，雌性受体几乎没有任何浸润的组织学迹象，即使在转移来自20周龄供体雄性的脾细胞后。这些观察结果为雄性性腺激素在NOD小鼠中的泪腺炎促进作用提供了强有力的证据，这一发现与已知的雄激素介导的对同一品系中的胰岛炎和下颌下炎以及对干燥综合征的其他动物模型中的泪腺炎的保护作用形成了对比。
Similar to pancreatic islets, submandibular glands are more rapidly infiltrated in female NOD mice than in males, The present comparative analysis of cellular infiltrations in lacrimal glands, however, revealed the opposite finding. At 12 wk of age, similar to 25% of male lacrimal tissue area is infiltrated, whereas age-matched female NOD mice still lack major signs of inflammation. T cells predominate in early stages of invasion, but B cells accumulate promptly in more advanced stages, and ultimately dominate over T cells, Dacryoadenitis is promoted by sex hormones, as suggested by the reduced infiltrations seen in orchidectomized NOD males (P < 0.01). It is also controlled by the local environment provided by the lacrimal tissue, Splenocytes from 4- and 20-wk-old female NOD mice cause massive lesions upon adoptive transfer into NOD male recipients while, conversely, female recipients develop barely any histological sign of infiltration, even after transfer of splenocytes from 20-wk-old donor males. These observations provide strong evidence for a dacryoadenitis-promoting role of male gonadal hormones in NOD mice, a finding that contrasts the known androgen-mediated protective effects on insulitis and submandibulitis in the same strain and on dacryoadenitis in other animal models of Sjogren's syndrome.