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Adipocytes control hematopoiesis and inflammation through CD40 signaling

Reiche, Myrthe E. (författare)
Uppsala universitet,Institutionen för medicinsk cellbiologi,Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.,Forskargrupp Gustaf Christoffersson
Poels, Kikkie (författare)
Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.
Bosmans, Laura A. (författare)
Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.
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Vos, Winnie G. (författare)
Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.
van Tiel, Claudia M. (författare)
Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.
Gijbels, Marion J. J. (författare)
Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.
Aarts, Suzanne A. B. M. (författare)
Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.
den Toom, Myrthe (författare)
Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.
Beckers, Linda (författare)
Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.
Weber, Christian (författare)
Maastricht Univ, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands.;Ludwig Maximilians Univ Munchen, Inst Cardiovasc Prevent IPEK, Munich, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany.
Atzler, Dorothee (författare)
Ludwig Maximilians Univ Munchen, Inst Cardiovasc Prevent IPEK, Munich, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany.;Ludwig Maximilians Univ Munchen, Walther Straub Inst Pharmacol & Toxicol, Munich, Germany.
Rensen, Patrick C. N. (författare)
Leiden Univ, Dept Med, Div Endocrinol, Med Ctr, Leiden, Netherlands. Leiden Univ, Einthoven Lab Vasc & Regenerat Med, Med Ctr, Leiden, 55902, Netherlands.
Kooijman, Sander (författare)
Leiden Univ, Dept Med, Div Endocrinol, Med Ctr, Leiden, Netherlands. Leiden Univ, Einthoven Lab Vasc & Regenerat Med, Med Ctr, Leiden, 55902, Netherlands.
Lutgens, Esther (författare)
Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Biochem, Amsterdam Cardiovasc Sci ACS, Amsterdam, Netherlands.;Ludwig Maximilians Univ Munchen, Inst Cardiovasc Prevent IPEK, Munich, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany.;Mayo Clin, Expt Cardiovasc Immunol Lab, Cardiovasc Med, Rochester, MN 55902 USA.
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 (creator_code:org_t)
2022-12-07
2023
Engelska.
Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 108:7, s. 1873-1885
Relaterad länk:
https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.3...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • The co-stimulatory CD40-CD40L dyad plays an important role in chronic inflammatory diseases associated with aging. Although CD40 is mainly expressed by immune cells, CD40 is also present on adipocytes. We aimed to delineate the role of adipocyte CD40 in the aging hematopoietic system and evaluated the effects of adipocyte CD40 deficiency on cardiometabolic diseases. Adult adipocyte CD40-deficient mice (AdiCD40KO) mice had a decrease in bone marrow hematopoietic stem cells (Lin-Sca+cKit+, LSK) and common lymphoid progenitors, which was associated with increased bone marrow adiposity and T-cell activation, along with elevated plasma corticosterone levels, a phenotype that became more pronounced with age. Atherosclerotic AdiCD40koApoE-/- (CD40AKO) mice also displayed changes in the LSK population, showing increased myeloid and lymphoid multipotent progenitors, and augmented corticosterone levels. Increased T-cell activation could be observed in bone marrow, spleen, and adipose tissue, while the numbers of B cells were decreased. Although atherosclerosis was reduced in CD40AKO mice, plaques contained more activated T cells and larger necrotic cores. Analysis of peripheral adipose tissue in a diet-induced model of obesity revealed that obese AdiCD40KO mice had increased T-cell activation in adipose tissue and lymphoid organs, but decreased weight gain and improved insulin sensitivity, along with increased fat oxidation. In conclusion, adipocyte CD40 plays an important role in maintaining immune cell homeostasis in bone marrow during aging and chronic inflammatory diseases, particularly of the lymphoid populations. Although adipocyte CD40 deficiency reduces atherosclerosis burden and ameliorates diet-induced obesity, the accompanying T-cell activation may eventually aggravate cardiometabolic diseases.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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