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Pre-diagnostic genotyping identifies T1D subjects with impaired Treg IL-2 signaling and an elevated proportion of FOXP3+IL-17+ cells
- Source :
- Genes & Immunity. 18:15-21
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- T-regulatory cells (Tregs) are essential for immune tolerance, and animal studies implicate their dysfunction in type 1 diabetes (T1D) pathogenesis. Tregs require interleukin-2 (IL-2) for their suppressive function, and variants in IL-2/IL-2R pathway genes have been associated with T1D. We previously reported that recent-onset T1D subjects have an increased population of FOXP3lo Tregs that secrete the pro-inflammatory cytokine, interleukin-17 (IL-17). We hypothesize that IL-2 signaling defects may drive T1D development by skewing protective Tregs towards an inflammatory Th17 phenotype. Overall, we found that the proportion of FOXP3+IL-17+ cells in T1D subjects pre-diagnosis was unchanged compared with healthy controls. However, stratification by IL2RA single-nucleotide polymorphisms revealed that T1D subjects with the rs3118470 CC risk variant have Tregs with IL-2 signaling defects and an increased proportion of FOXP3+IL-17+ cells before diagnosis. These data suggest a potential mechanism for genetically controlled loss of Treg function via dysfunctional IL-2 signaling in T1D.
- Subjects :
- 0301 basic medicine
Interleukin 2
Genotype
endocrine system diseases
medicine.medical_treatment
Immunology
Population
chemical and pharmacologic phenomena
Biology
T-Lymphocytes, Regulatory
Article
Immune tolerance
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Immune Tolerance
Genetics
medicine
Humans
education
Genetics (clinical)
education.field_of_study
Interleukin-17
nutritional and metabolic diseases
FOXP3
Forkhead Transcription Factors
hemic and immune systems
Flow Cytometry
Prognosis
Diabetes Mellitus, Type 1
030104 developmental biology
Cytokine
Interleukin-2
Th17 Cells
Interleukin 17
Signal transduction
Biomarkers
Signal Transduction
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 14765470 and 14664879
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Genes & Immunity
- Accession number :
- edsair.doi.dedup.....8121a17d679d2cf96b75a8834773bce4