近日,国际期刊《自然—免疫学》(Nature Immunology)报道了哈佛医学院等处研究人员的成果,他们发明了一种预测I型糖尿病(T1D)发作的方法。
T1D的研究模型采用的是非肥胖型糖尿病小鼠,但并非所有小鼠都会最终发展成末期糖尿病症状。Diane Mathis和同事使用了一种经过反复验证的磁共振成像技术来区分这些小鼠的糖尿病病情是否都发展为临床症状。利用该技术,他们还能估计出该病临床症状的发病时间。重要的是,他们注意到糖尿病的抗性与一种名为CRIg的受体有关:该受体通过巨噬细胞——一种免疫细胞的亚群——进行表达,对小鼠体内CRIg蛋白的控制可以降低糖尿病的发病率。
因为磁共振成像技术能应用于人体,所以下一步可在高危病人身上使用这种方法,以检验其能否作为T1D的预测工具。(生物谷Bioon.com)
doi:10.1038/ni.2233
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Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging
Wenxian Fu, Gregory Wojtkiewicz, Ralph Weissleder, Christophe Benoist & Diane Mathis
All juvenile mice of the nonobese diabetic (NOD) strain develop insulitis, but there is considerable variation in their progression to diabetes. Here we used a strategy based on magnetic resonance imaging (MRI) of magnetic nanoparticles to noninvasively visualize local effects of pancreatic-islet inflammation to predict the onset of diabetes in NOD mice. MRI signals acquired during a narrow early time window allowed us to sort mice into groups that would progress to clinical disease or not and to estimate the time to diabetes development. We exploited this approach to identify previously unknown molecular and cellular elements correlated with disease protection, including the complement receptor of the immunoglobulin superfamily (CRIg), which marked a subset of macrophages associated with diabetes resistance. Administration of a fusion of CRIg and the Fc portion of immunoglobulin resulted in lower MRI signals and diabetes incidence. In addition to identifying regulators of disease progression, we show here that diabetes is set at an early age in NOD mice.