Universität zu Köln

Nettersheim, Felix Sebastian, Braumann, Simon, Kobiyama, Kouji, Orecchioni, Marco, Vassallo, Melanie, Miller, Jacqueline, Ali, Amal, Roy, Payel, Saigusa, Ryosuke ORCID: 0000-0002-1640-6182, Wolf, Dennis ORCID: 0000-0003-1525-4348, Ley, Klaus and Winkels, Holger ORCID: 0000-0003-1333-2031 (2022). Autoimmune Regulator (AIRE) Deficiency Does Not Affect Atherosclerosis and CD4 T Cell Immune Tolerance to Apolipoprotein B. Front. Cardiovasc. Med., 8. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2297-055X

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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 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 ApoB peptide 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 overall inconsistent impacts on their phenotype. Furthermore, we show that atherosclerotic plaque size is not affected in Aire(-/-) Apoe(-/-) compared to Aire(+/+) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nettersheim, Felix Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Braumann, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Kobiyama, Kouji UNSPECIFIED UNSPECIFIED UNSPECIFIED Orecchioni, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Vassallo, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Miller, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Ali, Amal UNSPECIFIED UNSPECIFIED UNSPECIFIED Roy, Payel UNSPECIFIED UNSPECIFIED UNSPECIFIED Saigusa, Ryosuke UNSPECIFIED orcid.org/0000-0002-1640-6182 UNSPECIFIED Wolf, Dennis UNSPECIFIED orcid.org/0000-0003-1525-4348 UNSPECIFIED Ley, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkels, Holger UNSPECIFIED orcid.org/0000-0003-1333-2031 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-682910
DOI:	10.3389/fcvm.2021.812769
Journal or Publication Title:	Front. Cardiovasc. Med.
Volume:	8
Date:	2022
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	2297-055X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SELF-ANTIGEN EXPRESSION; SEX-DIFFERENCES; PROMOTES; FEATURES; THYMUS Multiple languages Cardiac & Cardiovascular Systems Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68291