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. doi: 10.1126/sciadv.adn2136. Epub 2024 May 17.

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 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.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1* / genetics
  • Diabetes Mellitus, Type 1* / immunology
  • Diabetes Mellitus, Type 1* / metabolism
  • Diabetes Mellitus, Type 1* / pathology
  • Disease Progression*
  • Female
  • Humans
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Male
  • Monocytes* / immunology
  • Monocytes* / metabolism
  • Young Adult