title: An unexpected intriguing effect of Toll-like receptor regulator RP105 (CD180) on atherosclerosis formation with alterations on B-cell activation.
abstract: OBJECTIVE
  In atherosclerosis, Toll-like receptors (TLRs) are traditionally linked to effects on tissue macrophages or foam cells. RP105, a structural TLR4 homolog, is an important regulator of TLR signaling. The effects of RP105 on TLR signaling vary for different leukocyte subsets known to be involved in atherosclerosis, making it unique in its role of either suppressing (in myeloid cells) or enhancing (in B cells) TLR-regulated inflammation in different cell types. We aimed to identify a role of TLR accessory molecule RP105 on circulating cells in atherosclerotic plaque formation.
  
  
  RESULTS
  Irradiated low density lipoprotein receptor deficient mice received RP105(-/-) or wild-type bone marrow. RP105(-/-) chimeras displayed a 57% reduced plaque burden. Interestingly, total and activated B-cell numbers were significantly reduced in RP105(-/-) chimeras. Activation of B1 B cells was unaltered, suggesting that RP105 deficiency only affected inflammatory B2 B cells. IgM levels were unaltered, but anti-oxidized low-density lipoprotein and anti-malondialdehyde-modified low-density lipoprotein IgG2c antibody levels were significantly lower in RP105(-/-) chimeras, confirming effects on B2 B cells rather than B1 B cells. Moreover, B-cell activating factor expression was reduced in spleens of RP105(-/-) chimeras.
  
  
  CONCLUSIONS
  RP105 deficiency on circulating cells results in an intriguing unexpected TLR-associated mechanisms that decrease atherosclerotic lesion formation with alterations on proinflammatory B2 B cells.
authors.affiliation: From the Department of Surgery (J.C.K., M.M.E., M.R.d.V., J.W.J., P.H.A.Q.), Einthoven Laboratory for Experimental Vascular Medicine (J.C.K., M.M.E., M.R.d.V., P.H.A.Q.), Department of Cardiology (M.M.E., J.W.J.), and Department of Immunohematology and Blood Transfusion (A.R., R.A.), Leiden University Medical Center, Leiden, The Netherlands; Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (S.C.A.d.J.); Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands (S.C.A.d.J., I.B., P.J.v.S., J.K.); Inserm U970, Paris Cardiovascular Research Center, Paris, France (Z.M.); Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria (C.J.B.); and Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria (C.J.B.).
authors.forename: J C
authors.initials: JC
authors.lastname: Karper
authors.forename: S C A
authors.initials: SC
authors.lastname: de Jager
authors.forename: M M
authors.initials: MM
authors.lastname: Ewing
authors.forename: M R
authors.initials: MR
authors.lastname: de Vries
authors.forename: I
authors.initials: I
authors.lastname: Bot
authors.forename: P J
authors.initials: PJ
authors.lastname: van Santbrink
authors.forename: A
authors.initials: A
authors.lastname: Redeker
authors.forename: Z
authors.initials: Z
authors.lastname: Mallat
authors.forename: C J
authors.initials: CJ
authors.lastname: Binder
authors.forename: R
authors.initials: R
authors.lastname: Arens
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
authors.forename: J
authors.initials: J
authors.lastname: Kuiper
authors.forename: P H A
authors.initials: PH
authors.lastname: Quax
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001011:Aorta / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D053264:B-Cell Activating Factor / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008077:Lipoproteins, LDL / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008315:Malondialdehyde / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic; D011828:Radiation Chimera; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; C490500:Ly78 protein, mouse; D011973:Receptors, LDL; C505720:Tnfsf13b protein, mouse; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde
keywords: B lymphocytes; Toll-like receptors; atherosclerosis; immune system; immunology; inflammation