Christoph J. Binder (Austria)

Medical University of Vienna Laboratory Medicine
Christoph J. Binder is an expert on the role of the immune system in atherosclerosis. He received his MD degree from the University of Vienna, Austria, and his PhD degree in Molecular Pathology from the University of California San Diego (UCSD), USA. Following an additional period of postdoctoral training at the Department of Medicine of UCSD, he returned to Vienna in 2005 to establish his own research group at the Department of Laboratory Medicine at the Medical University of Vienna. In 2009 he was appointed Full Professor of Atherosclerosis Research at the Medical University of Vienna. He is currently Deputy Head of the Department of Laboratory Medicine of the Medical University of Vienna. From 2006 until 2021 he was Principal Investigator at the Center for Molecular Medicine of the Austrian Academy of Sciences. Christoph Binder’s research interests span vascular biology, lipid oxidation, innate immunity, and cardiovascular disease. In particular his group is investigating immune mechanisms of atherosclerosis with a special focus on the role of innate and humoral immunity and how this can be exploited for the treatment of cardiovascular disease. His group first identified the atheroprotective role and mechanisms of IL-5, IL-13, and the B cell activating factor (BAFF) as well as of antigen-specific natural IgM antibodies. A major scientific focus of his work is the characterization of oxidation-specific epitopes (OSE), which are considered major drivers of the immuno-inflammatory process of atherosclerosis, as targets of humoral and cellular immunity. Christoph Binder has won numerous prestigious fellowships and awards and has authored >150 original and review papers in important international journals, including Nature and Nature Medicine. Since 2014 Christoph Binder acts as a referee and board member of the Austrian Science Fund (FWF). From 2016 until 2019 he was a member of the Executive Committee and since 2021 he is Vice President of the European Atherosclerosis Society.

Author Of 7 Presentations

Introduction to first session of the day (ID 1604)

Session Type
Plenary Session
Session Time
09:00 - 09:30
Date
Mon, 31.05.2021
Room
Live Streamed
Lecture Time
09:27 - 09:29

Humoral immune responses in the artery wall. (ID 1307)

Session Type
Vascular Biology
Session Time
10:30 - 12:00
Date
Tue, 01.06.2021
Room
Live Streamed
Lecture Time
11:03 - 11:18

Live Q&A (ID 1378)

Session Type
CME Session
Session Time
11:00 - 12:15
Date
Sun, 30.05.2021
Room
Hall A (Live Q&A)
Lecture Time
11:48 - 12:15

Live Q&A (ID 1434)

Session Type
Plenary Session
Session Time
17:30 - 19:00
Date
Tue, 01.06.2021
Room
Hall B (Live Q&A)
Lecture Time
18:30 - 19:00

Introduction (ID 1587)

Session Type
Plenary Session
Session Time
09:30 - 11:03
Date
Mon, 31.05.2021
Room
Live Streamed
Lecture Time
09:30 - 09:33

O026 - Histone methyltransferase DOT1L regulates macrophage inflammatory responses and lipid metabolism (ID 489)

Session Type
Vascular Biology
Session Time
16:00 - 17:30
Date
Mon, 31.05.2021
Room
Hall E
Lecture Time
16:54 - 17:02

Abstract

Background and Aims

DOT1L is the only histone methyltransferase for H3K79 and has recently emerged as a central player in the immune system.

Methods

Here we investigate the role of DOT1L in macrophages by application of a selective DOT1L inhibitor on either mouse or human macrophages and using myeloid-specific Dot1l deleted mice. Furthermore, we investigated myeloid Dot1l in vivo in a mouse model for atherosclerosis including scRNAseq on atherosclerotic plaques.

Results

Using RNA-seq and in vitro assays, we found that Dot1l represses macrophage activation and impacts cellular lipid metabolism. ChIP-seq for H3K79me revealed that DOT1L regulates H3K79 methylation of RXRα in macrophages, leading to reduced RXRα mRNA and protein expression, both upon Dot1l deletion as well as DOT1L inhibition. Given the established role for RXRα in controlling macrophage activation and lipid homeostasis, the phenotype we observe can thus be at least partly explained by impaired RXRα signaling. Moreover, we could induce a similar suppressed lipid phenotype using an RXRα antagonist in wild-type macrophages.

In vivo, we confirmed that myeloid Dot1l deletion increases the activation of plaque macrophages. Moreover, although plaque area was not affected, Dot1l deficiency led to enhanced necrosis, indicating potential plaque destabilization. Apart from these direct effects, we found that myeloid Dot1l also affects other immune cell subsets illustrated by reduced production of IgG and IgM antibodies targeting atherosclerosis-related antigens.

Conclusions

Our data show that myeloid DOT1L is a critical regulator of macrophage inflammatory responses and lipid homeostasis and that it impacts in vivo immune responses and atherosclerosis development.

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O035 - Phosphorylcholine-targeting vaccination reduces experimental atherosclerosis progression by expanding the B1-like specific B cell pool (ID 726)

Session Type
Vascular Biology
Session Time
10:30 - 12:00
Date
Tue, 01.06.2021
Room
Live Streamed
Lecture Time
11:34 - 11:42

Abstract

Background and Aims

Vaccination with phosphorylcholine (PC) reduces experimental atherosclerosis by raising the titer of PC-specific IgM in Apolipoprotein E knockout (ApoEKO) mice.

The epitope of the antibodies elicited by the PC-Vaccine coincides with that of 'natural' anti-pneumococcal antibodies and strikingly similar results can be obtained by vaccination with Prevenar®.

The aim of the present study was therefore to assess whether the atheroprotective effects carried by PC-Vaccine and Prevenar@ are linked to the activation of the germline encoded B cell pool, which is responsible for the production of natural antibodies.

Methods

AID Cre mice were crossed with ApoEKO mice and double transgenic mice were immunized with PC-Vaccine or with Prevenar® as previously reported (DOI:10.1016/j.atherosclerosis.2018.06.903). Three months later, atherosclerotic lesions and natural anti-PC IgM antibodies values were compared to the AID+ (affinity maturated) IgM+ (B1-like) cell pool in the peritoneal cavity and draining lymph nodes.

Results

Discriminant analysis showed that the rise of natural anti-PC IgM antibodies (AB1-2 IgM), the proportion of affinity matured (AID+) B1-like cells (CD19+ CD5+ CD43+ CD1d+ IgM+) having migrated from the draining lymph node to the peritoneal cavity and the lesion size (AUC) were interdependent from each other and that atheroprotection in both PC-Vaccine and Prevenar® mouse groups was proportional to the fraction of affinity matured B1-like cells in the peritoneal cavity and the rise of natural anti-PC IgM antibody production (individual data and bivariate plots are displayed in the figure).

via bivariate plots.jpg

Conclusions

Phosphorylcholine-targeting vaccination boosts affinity maturation of B lymphocytes involved in the production of natural antibodies and prevents experimental atherosclerosis progression.

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Presenter of 5 Presentations

Introduction (ID 1587)

Session Type
Plenary Session
Session Time
09:30 - 11:03
Date
Mon, 31.05.2021
Room
Live Streamed
Lecture Time
09:30 - 09:33

Introduction to first session of the day (ID 1604)

Session Type
Plenary Session
Session Time
09:00 - 09:30
Date
Mon, 31.05.2021
Room
Live Streamed
Lecture Time
09:27 - 09:29

Humoral immune responses in the artery wall. (ID 1307)

Session Type
Vascular Biology
Session Time
10:30 - 12:00
Date
Tue, 01.06.2021
Room
Live Streamed
Lecture Time
11:03 - 11:18

Live Q&A (ID 1378)

Session Type
CME Session
Session Time
11:00 - 12:15
Date
Sun, 30.05.2021
Room
Hall A (Live Q&A)
Lecture Time
11:48 - 12:15

Live Q&A (ID 1434)

Session Type
Plenary Session
Session Time
17:30 - 19:00
Date
Tue, 01.06.2021
Room
Hall B (Live Q&A)
Lecture Time
18:30 - 19:00