puc-header

c-Myb Exacerbates Atherosclerosis Through Regulation of Harmful B2 and Protective IgM-producing Antibody Secreting Cells

26 Pages Posted: 5 Apr 2018 Sneak Peek Status: Published

See all articles by Eric A. Shikatani

Eric A. Shikatani

University of Toronto - Department of Laboratory Medicine and Pathobiology

Rickvinder Besla

University of Toronto - Department of Laboratory Medicine and Pathobiology

Sherine Ensan

University of Toronto - Department of Immunology

Angela Li

University of Toronto - Department of Immunology

Norbert Degousee

University Health Network - Toronto General Research Institute (UHN Research)

Joshua M. Moreau

University of Toronto - Department of Immunology

Danya Thayaparan

McMaster University - McMaster Immunology Research Centre

Henry S. Cheng

University of Toronto - Department of Laboratory Medicine and Pathobiology

Shaun Pacheco

University Health Network - Toronto General Research Institute (UHN Research)

David Smyth

University Health Network - Toronto General Research Institute (UHN Research)

Hossein Noyan

University Health Network - Toronto General Research Institute (UHN Research)

Caleb CJ Zavitz

University Health Network - Toronto General Research Institute (UHN Research)

Carla M.T. Bauer

Hoffmann-La Roche, pRED - Roche Translational & Clinical Research Center (TCRC)

Ingo Hilgendorf

University of Frieburg - Department of Cardiology and Angiology I

Peter Libby

Harvard University - Department of Medicine

Filip K. Swirski

Harvard University - Center for Systems Biology (CSB)

Jennifer L. Gommerman

University of Toronto - Department of Immunology

Jason E. Fish

University of Toronto - Department of Laboratory Medicine and Pathobiology; University Health Network - Toronto General Research Institute (UHN Research)

Martin R. Stampfli

McMaster University - McMaster Immunology Research Centre

Myron Cybulsky

University of Toronto - Department of Laboratory Medicine and Pathobiology; University Health Network - Toronto General Research Institute (UHN Research); Peter Munk Cardiac Centre

Barry B. Rubin

Peter Munk Cardiac Centre

Christopher J. Paige

University of Toronto - Department of Immunology; University Health Network - Toronto General Research Institute (UHN Research); Ontario Institute for Cancer Research

Mansoor Husain

University of Toronto - Department of Laboratory Medicine and Pathobiology; University Health Network - Toronto General Research Institute (UHN Research); Ontario Institute for Cancer Research; McEwen Centre for Regenerative Medicine; Peter Munk Cardiac Centre

Clinton S. Robbins

University of Toronto - Department of Laboratory Medicine and Pathobiology; University of Toronto - Department of Immunology; University Health Network - Toronto General Research Institute (UHN Research); Peter Munk Cardiac Centre

More...

Abstract

Inflammation plays a key role in the development of atherosclerosis, yet transcriptional regulators of the inflammatory process remain largely unknown. Here, we identify the nuclear transcription factor c-Myb as a crucial mediator of atherosclerotic disease. Using mice harboring a c-Myb hypomorphic allele (c-Mybh: M303V), we demonstrate that c-Myb potentiates atherosclerosis directly through its effects on B cell development. Reduced c-Myb activity, we show, associated with decreased numbers of harmful B2 cells at multiple tissue sites. Paradoxically, inhibiting c-Myb elevated levels of atheroprotective OxLDL specific IgM antibodies and increased numbers of IgM-producing antibody secreting cells (IgM-ASC), identifying a novel function for c-Myb in regulating T cell-independent natural antibody responses. Thus, targeted disruption of c-Myb signaling represents a potential therapeutic approach that circumvents key aspects of the complex biology of B cells in cardiovascular disease.

Suggested Citation

Shikatani, Eric A. and Besla, Rickvinder and Ensan, Sherine and Li, Angela and Degousee, Norbert and Moreau, Joshua M. and Thayaparan, Danya and Cheng, Henry S. and Pacheco, Shaun and Smyth, David and Noyan, Hossein and Zavitz, Caleb CJ and Bauer, Carla M.T. and Hilgendorf, Ingo and Libby, Peter and Swirski, Filip K. and Gommerman, Jennifer L. and Fish, Jason E. and Stampfli, Martin R. and Cybulsky, Myron and Rubin, Barry B. and Paige, Christopher J. and Husain, Mansoor and Robbins, Clinton S., c-Myb Exacerbates Atherosclerosis Through Regulation of Harmful B2 and Protective IgM-producing Antibody Secreting Cells (2018). Available at SSRN: https://ssrn.com/abstract=3155580 or http://dx.doi.org/10.2139/ssrn.3155580
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Eric A. Shikatani

University of Toronto - Department of Laboratory Medicine and Pathobiology

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

Rickvinder Besla

University of Toronto - Department of Laboratory Medicine and Pathobiology

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

Sherine Ensan

University of Toronto - Department of Immunology

1 King's College Circle
Medical Sciences Building, Room 7207
Toronto, Ontario M5S 1A8
Canada

Angela Li

University of Toronto - Department of Immunology

1 King's College Circle
Medical Sciences Building, Room 7207
Toronto, Ontario M5S 1A8
Canada

Norbert Degousee

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Joshua M. Moreau

University of Toronto - Department of Immunology

1 King's College Circle
Medical Sciences Building, Room 7207
Toronto, Ontario M5S 1A8
Canada

Danya Thayaparan

McMaster University - McMaster Immunology Research Centre

1280 Main Street West
Hamilton, ON L8S 4K1
Canada

Henry S. Cheng

University of Toronto - Department of Laboratory Medicine and Pathobiology

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

Shaun Pacheco

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

David Smyth

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Hossein Noyan

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Caleb CJ Zavitz

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Carla M.T. Bauer

Hoffmann-La Roche, pRED - Roche Translational & Clinical Research Center (TCRC)

Nutley, NJ
United States

Ingo Hilgendorf

University of Frieburg - Department of Cardiology and Angiology I

Hugstetter Stra├če 55
79095 Freiburg
Germany

Peter Libby

Harvard University - Department of Medicine

Boston, MA 02115
United States

Filip K. Swirski

Harvard University - Center for Systems Biology (CSB)

Richard B. Simches Research Center
185 Cambridge Street, Suite 5.210
Boston, MA 02114
United States

Jennifer L. Gommerman

University of Toronto - Department of Immunology

1 King's College Circle
Medical Sciences Building, Room 7207
Toronto, Ontario M5S 1A8
Canada

Jason E. Fish

University of Toronto - Department of Laboratory Medicine and Pathobiology

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Martin R. Stampfli

McMaster University - McMaster Immunology Research Centre

1280 Main Street West
Hamilton, ON L8S 4K1
Canada

Myron Cybulsky

University of Toronto - Department of Laboratory Medicine and Pathobiology

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Peter Munk Cardiac Centre

585 University Avenue
Toronto, ON M5G 2N2
Canada

Barry B. Rubin

Peter Munk Cardiac Centre

585 University Avenue
Toronto, ON M5G 2N2
Canada

Christopher J. Paige

University of Toronto - Department of Immunology

1 King's College Circle
Medical Sciences Building, Room 7207
Toronto, Ontario M5S 1A8
Canada

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Ontario Institute for Cancer Research

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

Mansoor Husain

University of Toronto - Department of Laboratory Medicine and Pathobiology

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Ontario Institute for Cancer Research

661 University Avenue
Suite 510
Toronto, ON M5G 0A3
Canada

McEwen Centre for Regenerative Medicine

MaRS Centre, Toronto Medical Discovery Tower
101 College St. 8th Floor, room 701
Toronto, ON M5G 1L7
Canada

Peter Munk Cardiac Centre

585 University Avenue
Toronto, ON M5G 2N2
Canada

Clinton S. Robbins (Contact Author)

University of Toronto - Department of Laboratory Medicine and Pathobiology ( email )

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

University of Toronto - Department of Immunology ( email )

1 King's College Circle
Medical Sciences Building, Room 7207
Toronto, Ontario M5S 1A8
Canada

University Health Network - Toronto General Research Institute (UHN Research) ( email )

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Peter Munk Cardiac Centre ( email )

585 University Avenue
Toronto, ON M5G 2N2
Canada

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
277
Downloads
30