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Autoimmune Regulator (AIRE) Deficiency Does Not Affect Atherosclerosis and CD4 T Cell Immune Tolerance to Apolipoprotein B
- Source :
- Frontiers in Cardiovascular Medicine, Frontiers in Cardiovascular Medicine, Vol 8 (2022)
- Publication Year :
- 2021
-
Abstract
- Atherosclerosis is a chronic, lipid-driven disease of medium sized arteries which causes myocardial infarction and stroke. Recently, an adaptive immune response against the plaque-associated autoantigen Apolipoprotein B100 (ApoB), the structural protein component of low-density lipoprotein, has been implicated in atherogenesis. In healthy individuals, CD4+T cells responding to ApoB mainly comprised regulatory T cells, which confer immune tolerance and atheroprotection. Mice and patients with atherosclerosis harbor increased numbers of proatherogenic ApoB-reactive T-helper cell subsets. Given the lack of therapies targeting proatherogenic immunity, clarification of the underlying mechanisms is of high clinical relevance. T cells develop in the thymus, where strong autoreactive T cells are eliminated in the process of negative selection. Herein, we investigated whether the transcription factor autoimmune regulator (AIRE), which controls expression of numerous tissue-restricted self-antigens in the thymus, is involved in mediating tolerance to ApoB and whetherAiredeficiency might contribute to atherogenesis. Mice deficient forAirewere crossbred to apolipoprotein E-deficient mice to obtain atherosclerosis-proneAire−/−Apoe−/−mice, which were fed a regular chow diet (CD) or western-type diet (WD). CD4+T cells responding to the ApoB peptide p6 were analyzed by flow cytometry. We demonstrate thatAiredeficiency influences neither generation nor activation of ApoB-reactive T cells and has only minor and overall inconsistent impacts on their phenotype. Furthermore, we show that atherosclerotic plaque size is not affected inAire−/−Apoe−/−compared toAire+/+Apoe−/−, irrespective of diet and gender. In conclusion, our data suggests that AIRE is not involved in regulating thymic expression of ApoB or atherosclerosis. Alternative mechanisms how ApoB-reactive CD4 T cells are selected in the thymus will have to be investigated.
- Subjects :
- immune tolerance
T cells
autoimmune regulator
adaptive immunity
Cardiovascular Medicine
Brief Research Report
dextramer
thymic selection
antigen-specific
RC666-701
Diseases of the circulatory (Cardiovascular) system
lipids (amino acids, peptides, and proteins)
atherosclerosis
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 2297055X
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Frontiers in cardiovascular medicine
- Accession number :
- edsair.doi.dedup.....500c4e4b8b8621e7aa5f3cc7ddccd4bd