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| Status |
Public on Jan 01, 2024 |
| Title |
Monocytes in Type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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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| Overall design |
RNA was extracted from monocytes negatively selected from PBMC of 4 groups. 14 ROT1D samples were collected from subjects collected 2–7 months after diagnosis from subjects with histories of good glycemic control and possessed ≥1 autoantibody. Healthy control subjects were free of known infection at sample collection and belonged to one of the following 3 groups: 1) 15 HRSs - autoantibody-negative siblings of probands with high-risk (DR3 and/or DR4) HLA genotypes (HRS); 2) 19 LRSs - autoantibody-negative siblings of probands with lower risk (non-DR3/DR4) HLA genotypes (LRS); and 3) 14 uHCs - possessing no family history of T1D (uHC).
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| Contributor(s) |
Pant T, Lin C, Jia S, Roethle MF, Truchan NA, Bedrat A, Ciecko AE, Woodliff JE, Chen Y, Hessner MJ |
| Citation(s) |
38758799 |
| Submission date |
May 11, 2023 |
| Last update date |
May 30, 2024 |
| Contact name |
Martin Hessner |
| E-mail(s) |
mhessner@mcw.edu
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| Organization name |
Medical College of Wisconsin
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| Department |
Pediatrics
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| Lab |
Max McGee National Research Center for Juvenile Diabetes
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| Street address |
8701 Watertown Plank Road
|
| City |
Milwaukee |
| State/province |
WI |
| ZIP/Postal code |
53226 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (62)
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| Relations |
| BioProject |
PRJNA971595 |
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