Details

Autor(en) / Beteiligte

• Pant, Tarun
• Lin, Chien-Wei
• Bedrat, Amina
• Jia, Shuang
• Roethle, Mark F
• Truchan, Nathan A
• Ciecko, Ashley E
• Chen, Yi-Guang
• Hessner, Martin J

Titel

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

Ist Teil von

• Science advances, 2024-05, Vol.10 (20), p.eadn2136-eadn2136

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2024

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 CD14 CD16 HLADR KLRD1 PRF1 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.