Phagocytosis Deficiency of Macrophages in NOD.H-2h4 Mice Accelerates the Severity of Iodine-Induced Autoimmune Thyroiditis
Phagocytosis Deficiency of Macrophages in NOD.H-2h4 Mice Accelerates the Severity of Iodine-Induced Autoimmune Thyroiditis
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NOD.H-2h4 小鼠巨噬细胞吞噬功能缺陷会加速碘诱导的自身免疫性甲状腺炎的严重程度
DOI：
10.1007/s12011-017-1183-z
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Weiping Teng
中科院分区：
文献类型：
--
作者：
Xue He;Chuhui Xiong;Aihua Liu;Wei Zhao;Xinghai Xia;Shiqiao Peng;Chenyan Li;Mi Zhou;Yushu Li;Xiaoguang Shi;Zhongyan Shan;Weiping Teng
细胞凋亡发生在许多自身免疫性疾病中。过量的碘会诱导甲状腺细胞凋亡，并增加自身免疫性甲状腺炎（AIT）的发病率和患病率。然而，甲状腺细胞凋亡的出现和甲状腺炎的发生之间的事件顺序仍然未知。此外，很少有研究调查巨噬细胞吞噬作用在 AIT 发展中的作用。因此，我们通过比较组织样本中的事件序列来评估 NOD.H-2h4 小鼠甲状腺中细胞凋亡和炎症浸润之间的关系。我们还通过比较不同浓度碘处理的 BALB/c、C57BL/6 和 NOD.H-2h4 小鼠的巨噬细胞吞噬功能来研究巨噬细胞的作用。末端脱氧核苷酸转移酶 dUTP 缺口末端标记 (TUNEL) 检测和甲状腺炎症评分显示细胞凋亡（2 周）发生在炎症浸润（4 周）之前。细胞膜胞外表面的磷脂酰丝氨酸 (PS) 表达以及与细胞凋亡相关的双链 DNA 片段分别出现在第 2 周和第 8 周。此外，尽管补充过量碘的小鼠甲状腺细胞凋亡增强（BALB/c 为 0.05 ± 0.12 vs 1.63 ± 0.82%，C57BL/6 为 0.09 ± 0.14 vs 1.51 ± 0.34%，C57BL/6 为 0.07 ± 1.11 vs 4.72 ± 0.62%） NOD.H-2h4 小鼠），仅 NOD.H-2h4 小鼠甲状腺出现炎症。此外，与 BALB/c (54.21 ± 4.58%) 和 C57BL/6 (58.96 ± 4.04%) 小鼠相比，NOD.H-2h4 小鼠 (44.46 ± 1.79%) 的巨噬细胞的吞噬活性降低。补充过量碘或未治疗的 NOD.H-2h4 小鼠之间的吞噬功能没有差异（24.50 ± 2.66 vs 21.71 ± 1.79%，p = 0.06）。总之，NOD.H-2h4小鼠巨噬细胞凋亡清除的缺陷可能构成AIT的早期致病机制，且不受碘摄入的影响。
Apoptosis occurs in many autoimmune diseases. Excess iodine induces thyrocyte apoptosis and increases the incidence and prevalence of autoimmune thyroiditis (AIT). However, the sequence of events between the appearance of thyrocyte apoptosis and the occurrence of thyroiditis remains uncharacterized. Furthermore, few studies have investigated the role of macrophage phagocytosis in the development of AIT. Therefore, we evaluated the relationship between apoptosis and inflammatory infiltration in NOD.H-2h4 mouse thyroids by comparing the sequence of events in tissue samples. We also investigated the role of macrophages by comparing macrophage phagocytosis function in BALB/c, C57BL/6, and NOD.H-2h4 mice treated with different levels of iodine. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays and thyroid inflammatory scores revealed that apoptosis (2 weeks) occurred before inflammatory infiltration (4 weeks). Phosphatidylserine (PS) expression on the extracellular surface of the cell membrane and double-stranded DNA fragments associated with apoptosis appeared at 2 and 8 weeks, respectively. Additionally, although apoptosis was enhanced in the thyroids of mice supplemented with excess iodine (0.05 ± 0.12 vs 1.63 ± 0.82% for BALB/c, 0.09 ± 0.14 vs 1.51 ± 0.34% for C57BL/6, and 0.07 ± 1.11 vs 4.72 ± 0.62% for NOD.H-2h4 mice), only NOD.H-2h4 mouse thyroids presented with inflammation. Furthermore, macrophages from NOD.H-2h4 mice (44.46 ± 1.79%) exhibited decreased phagocytotic activity relative to that in BALB/c (54.21 ± 4.58%) and C57BL/6 (58.96 ± 4.04%) mice. There were no differences in phagocytosis function between NOD.H-2h4 mice supplemented with excess iodine or left untreated (24.50 ± 2.66 vs 21.71 ± 1.79%, p = 0.06). In conclusion, deficiencies in the apoptosis clearance of macrophages in NOD.H-2h4 mice may constitute an early pathogenic mechanism in AIT that is not influenced by iodine intake.
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影响因子：
7.7
作者：
B. O'Brien;B. Harmon;D. Cameron;D. Allan
通讯作者：
B. O'Brien;B. Harmon;D. Cameron;D. Allan
影响因子：
5.8
作者：
Shi, Xiaoguang;Han, Cheng;Teng, Weiping
通讯作者：
Teng, Weiping
自身免疫性甲状腺疾病患者中 Toll 样受体活性和 TLR 配体增加
影响因子：
7.3
作者：
Peng S;Li C;Wang X;Liu X;Han C;Jin T;Liu S;Zhang X;Zhang H;He X;Xie X;Yu X;Wang C;Shan L;Fan C;Shan Z;Teng W
通讯作者：
Teng W
影响因子：
12.8
作者：
O'Brien, BA;Geng, X;Dutz, JP
通讯作者：
Dutz, JP
DOI：
10.1073/pnas.96.5.2285
发表时间：
1999-03-02
影响因子：
11.1
作者：
Suzuki, K;Mori, A;Kohn, LD
通讯作者：
Kohn, LD