c-Myb exacerbates atherosclerosis through regulation of protective IgM-producing antibody-secreting cells

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Abstract: Mechanisms that govern transcriptional regulation of inflammation in atherosclerosis remain largely unknown. Here, we identify the nuclear transcription factor c-Myb as an important mediator of atherosclerotic disease in mice. Atherosclerosis-prone animals fed a diet high in cholesterol exhibit increased levels of c-Myb in the bone marrow. Use of mice that either harbor a c-Myb hypomorphic allele or where c-Myb has been preferentially deleted in B cell lineages revealed that c-Myb potentiates atherosclerosis directly through its effects on B lymphocytes. Reduced c-Myb activity prevents the expansion of atherogenic B2 cells yet associates with increased numbers of IgM-producing antibody-secreting cells (IgM-ASCs) and elevated levels of atheroprotective oxidized low-density lipoprotein (OxLDL)-specific IgM antibodies. Transcriptional profiling revealed that c-Myb has a limited effect on B cell function but is integral in maintaining B cell progenitor populations in the bone marrow. Thus, targeted disruption of c-Myb beneficially modulates the complex biology of B cells in cardiovascular disease

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
issn: 2211-1247

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2019
Urheber
Shikatani, Eric A
Besla, Rickvinder
Ensan, Sherine
Upadhye, Aditi
Khyzha, Nadiya
Li, Angela
Emoto, Takuo
Chiu, Felix
Degousee, Norbert
Moreau, Joshua M.
Perry, Heather M.
Thayaparan, Danya
Cheng, Henry S.
Pacheco, Shaun
Smyth, David
Noyan, Hossein
Zavitz, Caleb C. J.
Bauer, Carla M. T.
Hilgendorf, Ingo
Libby, Peter
Swirski, Filip K.
Gommerman, Jennifer L.
Fish, Jason E.
Stampfli, Martin R.
Cybulsky, Myron I.
Rubin, Barry B.
Paige, Christopher J.
Bender, Timothy P.
McNamara, Coleen A.
Husain, Mansoor
Robbins, Clinton S.

DOI
10.1016/j.celrep.2019.04.090
URN
urn:nbn:de:bsz:25-freidok-1498507
Rechteinformation
Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:35 MESZ

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Beteiligte

  • Shikatani, Eric A
  • Besla, Rickvinder
  • Ensan, Sherine
  • Upadhye, Aditi
  • Khyzha, Nadiya
  • Li, Angela
  • Emoto, Takuo
  • Chiu, Felix
  • Degousee, Norbert
  • Moreau, Joshua M.
  • Perry, Heather M.
  • Thayaparan, Danya
  • Cheng, Henry S.
  • Pacheco, Shaun
  • Smyth, David
  • Noyan, Hossein
  • Zavitz, Caleb C. J.
  • Bauer, Carla M. T.
  • Hilgendorf, Ingo
  • Libby, Peter
  • Swirski, Filip K.
  • Gommerman, Jennifer L.
  • Fish, Jason E.
  • Stampfli, Martin R.
  • Cybulsky, Myron I.
  • Rubin, Barry B.
  • Paige, Christopher J.
  • Bender, Timothy P.
  • McNamara, Coleen A.
  • Husain, Mansoor
  • Robbins, Clinton S.
  • Universität

Entstanden

  • 2019

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