Monocytes in type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression.
Sci Adv
; 10(20): eadn2136, 2024 May 17.
Article
in En
| MEDLINE
| ID: mdl-38758799
ABSTRACT
Monocytes are immune regulators implicated in the pathogenesis of type 1 diabetes (T1D), an autoimmune disease that targets insulin-producing pancreatic ß 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 ß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
Disease Progression
/
Diabetes Mellitus, Type 1
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Sci Adv
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos