Defective expression of regulatory B cells in iodine-induced autoimmune thyroiditis in non-obese diabetic H-2h4 mice
Defective expression of regulatory B cells in iodine-induced autoimmune thyroiditis in non-obese diabetic H-2h4 mice
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DOI：
10.1007/s40618-013-0013-1
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发表时间：
2014-01-01
影响因子：
5.4
通讯作者：
Teng, W.
中科院分区：
文献类型：
--
作者：
Shi, L.;Bi, M.;Teng, W.
引言B细胞负调节细胞免疫应答和炎症的能力已被描述。调节性B（布雷格）细胞具有独特的CD 1d（hi）CD 5（+）CD 19（+）表型和产生IL-10的能力，在几种体内自身免疫性疾病小鼠模型中是炎症和自身免疫的有效负调节因子。将4周龄的小鼠随机分为对照组和碘处理组;碘处理组接受含0.005%NaI的无菌水10或20周。流式细胞术检测脾单个核细胞中CD 1d（hi）、CD 5（+）、CD 19（+）、CD 4（+）、CD 25（+）、FoxP 3（+）调节性T细胞（Treg）和CD 4（+）、IL 17（+）、辅助性T细胞（Th 17）的百分比。结果NOD.H-2（h4）小鼠在饮水加碘后自发产生抗甲状腺球蛋白自身抗体和甲状腺内淋巴细胞浸润。与对照组相比，AIT小鼠脾细胞中的CD 1d（hi）、CD 5（+）、CD 19（+）布雷格亚群和IL-10 mRNA表达降低（p < 0.05），并在甲状腺炎的发展过程中维持相对较低的水平。结论NOD.H-2（h4）小鼠脾细胞中布雷格细胞表达缺陷、Treg细胞受损和Th 17细胞增强可能在碘诱导的AIT发生中起重要作用。
Introduction The ability of B cells to negatively regulate cellular immune responses and inflammation has been described. The regulatory B (Breg) cells with the unique CD1d(hi)CD5(+)CD19(+) phenotype and the capacity to produce IL-10 are potent negative regulators of inflammation and autoimmunity in several in vivo mouse models of autoimmune disease.Aim To investigate whether Breg cell deficiency participates in autoimmune thyroiditis (AIT) in an animal model.Materials and methods Non-obese diabetic (NOD).H-2(h4) mice at 4 weeks of age were randomly divided into control and iodine-treated groups; the iodine-treated group received sterile water containing 0.005 % NaI for 10 or 20 weeks. The percentage of CD1d(hi)CD5(+)CD19(+) Bregs, CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg) and CD4(+)IL17(+) T helper 17 cells (Th17) in splenic mononuclear cells was detected by multicolor flow cytometry. The expression of IL-10 mRNA and TGF-beta mRNA in splenocytes was measured by real-time RT-PCR.Results NOD.H-2(h4) mice spontaneously develop anti-thyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in drinking water. Mice with AIT had a decreased CD1d(hi)CD5(+)CD19(+) Breg subset and reduced IL-10 mRNA expression in splenocytes compared with controls (p < 0.05) and maintained relatively low levels during the development of thyroiditis. The proportion of Breg cells was negatively correlated with the proportion of Th17 cells, but positively correlated with CD4(+)CD25(+)FoxP3(+) Treg cells in splenocytes (All p < 0.05).Conclusions The defective expression of Breg cells combined with impaired Treg cells and enhanced Th17 cells might play an important role in the development of iodine-induced AIT in NOD.H-2(h4) mice.