Interleukin-12 exacerbates Sjogren's syndrome through induction of myeloid-derived suppressor cells
Interleukin-12 exacerbates Sjogren's syndrome through induction of myeloid-derived suppressor cells
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Interleukin-12 通过诱导骨髓源性抑制细胞加剧干燥综合征
DOI：
10.3892/mmr.2019.10352
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发表时间：
2019-08-01
影响因子：
3.4
通讯作者：
Hou, Yayi
中科院分区：
文献类型：
--
作者：
Qi, Jingjing;Li, Dan;Hou, Yayi
白细胞介素（IL）-12调节各种免疫细胞的产生和功能，在干燥综合征（SS）的发病机制中起着重要作用。骨髓源性抑制细胞（MDSC）通过调节各种免疫反应参与自身免疫性疾病。然而，尚未证实炎性IL-12是否通过调节MSDCs参与SS的进展。采用ELISA法检测SS样非肥胖糖尿病（NOD）小鼠血浆IL-12水平。分别腹腔注射IL-12和抗IL-12抗体，检测唾液流率。在苏木精和伊红染色的组织切片中评价下颌下腺的病理学。通过流式细胞术评估MDSC的比例。结果显示，SS样NOD小鼠血浆IL-12水平明显高于对照组。外源性IL-12可加重NOD小鼠的SS样症状，并促进SS样NOD小鼠骨髓和脾脏MDSC的生成。值得注意的是，抗IL-12减轻了NOD小鼠的SS样症状，并抑制了BM和脾MDSC的产生。此外，在IL-12缺陷型C57 BL/6（IL-12（-/-）B6）小鼠中MDSC的产生被削弱。我们的研究结果表明，SS样症状的加重，IL-12在NOD小鼠可能是由于其促进MDSC的发展。
Interleukin (IL)-12 modulates the generation and function of various immune cells and plays a vital role in the pathogenesis of Sjogren's syndrome (SS). Myeloid-derived suppressor cells (MDSCs) are involved in autoimmune diseases by regulating various immune responses. However, it has not been confirmed whether inflammatory IL-12 participates in the progression of SS via regulating MSDCs. In the present study, the plasma levels of IL-12 were detected by ELISA in SS-like non-obese diabetic (NOD) mice. The mice were treated by intraperitoneal injection of IL-12 and anti-IL-12 antibody, respectively, and then the salivary flow rate was detected. The pathology of submandibular glands was evaluated in tissue sections stained with hematoxylin and eosin. The proportion of MDSCs was assessed by flow cytometry. The results showed that plasma IL-12 was significantly increased in the SS-like NOD mice comparing with that noted in the control mice. The exogenous IL-12 exacerbated SS-like symptoms of NOD mice and promoted the generation of both bone marrow (BM) and splenic MDSCs in the SS-like NOD mice. Of note, anti-IL-12 alleviated SS-like symptoms of NOD mice and inhibited the generation of BM and splenic MDSCs. Moreover, the generation of MDSCs was crippled in the IL-12-deficient C57BL/6 (Il-12(-/-) B6) mice. Our findings suggest that aggravation of SS-like symptoms by IL-12 in NOD mice may be attributed to its promotion of MDSC development.