Sharma Rajni B, Alegria Judy D, Talor Monica V, Rose Noel R, Caturegli Patrizio, Burek C Lynne
Department of Pathology, School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
J Immunol. 2005 Jun 15;174(12):7740-5. doi: 10.4049/jimmunol.174.12.7740.
NOD.H2(h4) mice spontaneously develop autoimmune lymphocytic thyroiditis that mimics human Hashimoto's thyroiditis, a disease where iodine, IFN-gamma, and adhesion molecules have all been implicated in the pathogenesis. To study how iodine and IFN-gamma modulate the expression of ICAM-1, we analyzed NOD.H2(h4) thyrocytes in baseline conditions (day 0) and at several time points following supplementation of iodine in the drinking water. On day 0, a small percentage ( approximately 10%) of thyrocytes constitutively expressed ICAM-1. The expression gradually increased to 13, 25, and 41% on days 7, 14 and 28, respectively, returning to baseline (9%) on day 35. The initial ICAM-1 kinetics was paralleled by thyroidal infiltration of CD45(+) hemopoietic cells, which increased from an average of 4% on day 0 to an average of 13, 21, and 24% on days 14, 28, and 35, respectively. To distinguish whether the observed ICAM-1 increase was a direct effect of iodine or a consequence of the immune infiltrate, we treated mouse primary thyrocyte cultures with 0.01 mM sodium iodine and showed a 3-fold increased ICAM-1 expression. To assess interaction between IFN-gamma and iodine, we analyzed CD45 and ICAM-1expression on thyrocytes from NOD.H2(h4) wild-type and NOD.H2(h4) thyr-IFN-gamma transgenic littermates. Strikingly, IFN-gamma interacted synergistically with iodine to enhance ICAM-1 expression on thyrocytes. These findings suggest that iodine and IFN-gamma cooperate to promote thyroidal expression of ICAM-1 in this mouse model of thyroiditis, highlighting the complex interplay present in the pathogenesis of Hashimoto's thyroiditis.
NOD.H2(h4)小鼠会自发发展出自身免疫性淋巴细胞性甲状腺炎，这种疾病类似于人类的桥本甲状腺炎，在该疾病的发病机制中，碘、干扰素-γ和黏附分子都有涉及。为了研究碘和干扰素-γ如何调节细胞间黏附分子-1（ICAM-1）的表达，我们分析了处于基线状态（第0天）以及在饮用水中补充碘后的几个时间点的NOD.H2(h4)甲状腺细胞。在第0天，一小部分（约10%）的甲状腺细胞组成性表达ICAM-1。其表达在第7天、第14天和第28天分别逐渐增加到13%、25%和41%，在第35天恢复到基线水平（9%）。最初的ICAM-1动力学变化与CD45(+)造血细胞的甲状腺浸润情况平行，CD45(+)造血细胞的浸润率从第0天的平均4%分别增加到第14天、第28天和第35天的平均13%、21%和24%。为了区分观察到的ICAM-1增加是碘的直接作用还是免疫浸润的结果，我们用0.01 mM碘化钠处理小鼠原代甲状腺细胞培养物，结果显示ICAM-1表达增加了3倍。为了评估干扰素-γ与碘之间的相互作用，我们分析了NOD.H2(h4)野生型和NOD.H2(h4)甲状腺-干扰素-γ转基因同窝小鼠甲状腺细胞上的CD45和ICAM-1表达。令人惊讶的是，干扰素-γ与碘协同作用，增强了甲状腺细胞上ICAM-1的表达。这些发现表明，在这个甲状腺炎小鼠模型中，碘和干扰素-γ共同促进甲状腺中ICAM-1的表达，突出了桥本甲状腺炎发病机制中存在的复杂相互作用。
