Institute of Clinical Laboratory Science, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu 210002, P.R. China.
Shanghai Public Health Clinical Center, Fudan University, Shanghai 200000, P.R. China.
Mol Med Rep. 2019 Jun;19(6):5377-5385. doi: 10.3892/mmr.2019.10195. Epub 2019 Apr 25.
Hyperglycemia promotes the growth and reproduction of bacteria, thereby increasing the probability of infection, which also causes rebound hyperglycemia. Therefore, the interactions of infection and hyperglycemia lead to the progression and deterioration of these diseases. Type 1 diabetes mellitus (T1DM) is an autoimmune disease. Studies have shown that regulatory T cells (Tregs) play a key role in maintaining islet‑specific tolerance. Treg deficiency may lead to the development of early pancreatitis and T1DM, and sufficient amounts of Tregs can restore this tolerance, thereby inhibiting the occurrence of T1DM. Moreover, different subpopulations of dendritic cells (DCs) play an important role in activating autoreactive T cells and inducing autoimmune tolerance to autoantigens, which are closely related to the functional diversity caused by different phenotypes, maturation status, and the immune microenvironment of DC subpopulations. In the present study, we used streptozotocin‑induced hyperglycemic mice to model T1DM and induced a Salmonella infection in the mouse model, leading to aggravated inflammation, which resulted in an elevated proportion of CD103+CD11b+ DCs and a significantly elevated proportion of CD4+FoxP3+ Tregs in the intestinal lamina propria. After co‑culturing CD4+ T cells and DCs, we found that CD103+CD11b+ DCs could significantly promote the proliferation of CD4+ T cells. The elevated proportions of CD4+FoxP3+ Tregs were considered to be correlated with the increased number of CD103+CD11b+ DCs.
高血糖会促进细菌的生长和繁殖,从而增加感染的概率,这也会导致血糖反弹。因此,感染和高血糖的相互作用导致这些疾病的进展和恶化。1 型糖尿病(T1DM)是一种自身免疫性疾病。研究表明,调节性 T 细胞(Tregs)在维持胰岛特异性耐受中起关键作用。Treg 缺乏可能导致早期胰腺炎和 T1DM 的发生,而充足数量的 Tregs 可以恢复这种耐受,从而抑制 T1DM 的发生。此外,树突状细胞(DC)的不同亚群在激活自身反应性 T 细胞和诱导自身抗原的自身免疫耐受方面发挥重要作用,这与 DC 亚群的不同表型、成熟状态和免疫微环境引起的功能多样性密切相关。在本研究中,我们使用链脲佐菌素诱导的高血糖小鼠模型来模拟 T1DM,并在小鼠模型中诱导沙门氏菌感染,导致炎症加重,从而导致肠道固有层中 CD103+CD11b+ DCs 的比例升高和 CD4+FoxP3+ Tregs 的比例显著升高。在共培养 CD4+T 细胞和 DC 后,我们发现 CD103+CD11b+ DCs 可显著促进 CD4+T 细胞的增殖。CD4+FoxP3+ Tregs 的比例升高被认为与 CD103+CD11b+ DCs 的数量增加有关。