AUTHOR=Nettersheim Felix Sebastian , Braumann Simon , Kobiyama Kouji , Orecchioni Marco , Vassallo Melanie , Miller Jacqueline , Ali Amal , Roy Payel , Saigusa Ryosuke , Wolf Dennis , Ley Klaus , Winkels Holger 

TITLE=Autoimmune Regulator (AIRE) Deficiency Does Not Affect Atherosclerosis and CD4 T Cell Immune Tolerance to Apolipoprotein B

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.812769

DOI=10.3389/fcvm.2021.812769

ISSN=2297-055X

ABSTRACT=Atherosclerosis is a chronic, lipid-driven disease of medium sized arteries which causes myocardial infarction and stroke. Adaptive immune responses against the plaque-associated autoantigen Apolipoprotein B100 (ApoB), the structural protein component of low-density lipoprotein, have been implicated in atherogenesis. In healthy individuals, CD4+ T cells responding to ApoB were mainly FoxP3+ 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. 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 whether Aire deficiency might contribute to atherogenesis. Mice deficient for AIRE were crossbred to apolipoprotein E-deficient mice to obtain atherosclerosis-prone Aire-/- Apoe-/- mice, which were fed a regular chow diet (CD) or western-type diet (WD). CD4+ T cells responding to the ApoB978-993 peptide epitope p6  were analyzed by flow cytometry. We demonstrate that AIRE deficiency influences neither generation nor activation of ApoB-reactive T cells and has only minor and impact on their phenotype. Furthermore, we show that atherosclerotic plaque size is not different in Aire-/- Apoe-/-  compared to Aire+/+ Apoe-/-, irrespective of diet and sex. In conclusion, our data suggests that AIRE is not involved in regulating thymic expression of ApoB  or atherosclerosis.