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

ABSTRACT: Monocytes are immune regulators implicated in the pathogenesis of Type 1 diabetes (T1D), an autoimmune disease that targets the insulin-producing pancreatic β-cell. We determined that monocytes of recent onset (RO) T1D patients and their healthy siblings express proinflammatory/cytolytic transcriptomes and hyper-secrete cytokines in response to lipopolysaccharide exposure compared to unrelated healthy controls (uHC). Flow cytometry measured elevated circulating abundances of intermediate monocytes and >2-fold more CD14+CD16+HLADR+KLRD1+PRF1+ NK-like monocytes among ROT1D patients 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 post-onset. Among sibling non-progressors, flow cytometry measured temporal decreases in the intermediate to nonclassical monocyte ratio and NK-like monocyte abundances; these changes coincided with increases in peripheral 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE232310 | GEO | 2024/01/01

REPOSITORIES: GEO

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

Project description:Monocytes are immune regulators implicated in the pathogenesis of Type 1 diabetes (T1D), an autoimmune disease that targets the insulin-producing pancreatic β-cell. We determined that monocytes of recent onset (RO) T1D patients and their healthy siblings express proinflammatory/cytolytic transcriptomes and hyper-secrete cytokines in response to lipopolysaccharide exposure compared to unrelated healthy controls (uHC). Flow cytometry measured elevated circulating abundances of intermediate monocytes and >2-fold more CD14+CD16+HLADR+KLRD1+PRF1+ NK-like monocytes among ROT1D patients 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 post-onset. Among sibling non-progressors, flow cytometry measured temporal decreases in the intermediate to nonclassical monocyte ratio and NK-like monocyte abundances; these changes coincided with increases in peripheral 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.

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Gene expression profiling of the classical (CD14++CD16-), intermediate (CD14++CD16+) and nonclassical (CD14+CD16+) human monocyte subsets

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