Monocytes in type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression. Sci Adv 2024 May 17;10(20):eadn2136
Date
05/17/2024Pubmed ID
38758799Pubmed Central ID
PMC11100571DOI
10.1126/sciadv.adn2136Scopus ID
2-s2.0-85193631768 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
Author List
Pant T, Lin CW, Bedrat A, Jia S, Roethle MF, Truchan NA, Ciecko AE, Chen YG, Hessner MJAuthors
Amina Bedrat Postdoctoral Researcher 4 in the Pediatrics department at Medical College of WisconsinYi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
Shuang Jia Biostatistician III in the Pediatrics department at Medical College of Wisconsin
Chien-Wei Lin PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin
Tarun Pant Postdoctoral Researcher 4 in the Surgery department at Medical College of Wisconsin
Nathan A. Truchan Research Scientist I in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdolescentAdult
Case-Control Studies
Child
Cytokines
Diabetes Mellitus, Type 1
Disease Progression
Female
Humans
Insulin-Secreting Cells
Killer Cells, Natural
Male
Monocytes
Young Adult
