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1 型糖尿病家族中的单核细胞表现出高细胞溶解活性和亚群丰度，与临床进展相关。

Monocytes in type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression.

机构信息

The Max McGee Research Center for Juvenile Diabetes, Children's Research Institute of Children's Hospital of Wisconsin, Milwaukee, WI, USA.

Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, WI, USA.

出版信息

Sci Adv. 2024 May 17;10(20):eadn2136. doi: 10.1126/sciadv.adn2136.

DOI:10.1126/sciadv.adn2136
PMID:38758799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11100571/
Abstract

Monocytes are immune regulators implicated in the pathogenesis of type 1 diabetes (T1D), an autoimmune disease that targets insulin-producing pancreatic β cells. We determined that monocytes of recent onset (RO) T1D patients and their healthy siblings express proinflammatory/cytolytic transcriptomes and hypersecrete cytokines in response to lipopolysaccharide exposure compared to unrelated healthy controls (uHCs). Flow cytometry measured elevated circulating abundances of intermediate monocytes and >2-fold more CD14CD16HLADRKLRD1PRF1 NK-like monocytes among patients with ROT1D compared to uHC. The intermediate to nonclassical monocyte ratio among ROT1D patients correlated with the decline in functional β cell mass during the first 24 months after onset. Among sibling nonprogressors, temporal decreases were measured in the intermediate to nonclassical monocyte ratio and NK-like monocyte abundances; these changes coincided with increases in activated regulatory T cells. In contrast, these monocyte populations exhibited stability among T1D progressors. This study associates heightened monocyte proinflammatory/cytolytic activity with T1D susceptibility and progression and offers insight to the age-dependent decline in T1D susceptibility.

摘要

单核细胞是免疫调节因子，参与 1 型糖尿病（T1D）的发病机制，T1D 是一种自身免疫性疾病，其靶标是产生胰岛素的胰腺β细胞。我们发现，与无亲缘关系的健康对照者（uHC）相比，近期发病（RO）T1D 患者及其健康兄弟姐妹的单核细胞表达促炎/细胞溶解的转录组，并在脂多糖暴露下过度分泌细胞因子。流式细胞术测量显示，与 uHC 相比，RO T1D 患者的循环中间单核细胞和 CD14CD16HLADRKLRD1PRF1 NK 样单核细胞的含量增加了两倍以上。RO T1D 患者中间至非经典单核细胞比例与发病后 24 个月内功能性β细胞群的下降相关。在非进展性兄弟姐妹中，中间至非经典单核细胞比例和 NK 样单核细胞含量呈时间性下降；这些变化与活化的调节性 T 细胞的增加相吻合。相比之下，这些单核细胞群在 T1D 进展者中表现出稳定性。本研究将单核细胞的促炎/细胞溶解活性与 T1D 的易感性和进展相关联，并为 T1D 易感性随年龄下降提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4a/11100571/16783d1a84b4/sciadv.adn2136-f9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4a/11100571/a62e6eef1bec/sciadv.adn2136-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4a/11100571/16783d1a84b4/sciadv.adn2136-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4a/11100571/a789e53c8bc8/sciadv.adn2136-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4a/11100571/c65409139302/sciadv.adn2136-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4a/11100571/3331b5038bce/sciadv.adn2136-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4a/11100571/2ea3aa127e0e/sciadv.adn2136-f7.jpg
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