Age-associated accumulation of B cells promotes macrophage inflammation and inhibits lipolysis in adipose tissue during sepsis

Anna Carey; Katie Nguyen; Pranathi Kandikonda; Victor Kruglov; Claire Bradley; Korbyn J.V. Dahlquist; Stephanie Cholensky; Whitney Swanson; Vladimir P. Badovinac; Thomas S. Griffith; Christina D. Camell

Cell Reports (Mar 2024)

Age-associated accumulation of B cells promotes macrophage inflammation and inhibits lipolysis in adipose tissue during sepsis

Anna Carey,
Katie Nguyen,
Pranathi Kandikonda,
Victor Kruglov,
Claire Bradley,
Korbyn J.V. Dahlquist,
Stephanie Cholensky,
Whitney Swanson,
Vladimir P. Badovinac,
Thomas S. Griffith,
Christina D. Camell

Affiliations

Anna Carey: Molecular Pharmacology and Therapeutics Graduate Program, Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Katie Nguyen: Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Pranathi Kandikonda: Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Victor Kruglov: Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Claire Bradley: Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Korbyn J.V. Dahlquist: Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Stephanie Cholensky: Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Whitney Swanson: Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA
Vladimir P. Badovinac: Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Thomas S. Griffith: Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA; Minneapolis VA Health Care System, Minneapolis, MN 55417, USA
Christina D. Camell: Molecular Pharmacology and Therapeutics Graduate Program, Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 3
p. 113967

Abstract

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Summary: Non-canonical lipolysis induced by inflammatory cytokines or Toll-like receptor ligands is required for the regulation of inflammation during endotoxemia and sepsis. Canonical lipolysis induced by catecholamines declines during aging due to factors including an expansion of lymphocytes, pro-inflammatory macrophage polarization, and an increase in chronic low-grade inflammation; however, the extent to which the non-canonical pathway of lipolysis is active and impacted by immune cells during aging remains unclear. Therefore, we aimed to define the extent to which immune cells from old mice influence non-canonical lipolysis during sepsis. We identified age-associated impairments of non-canonical lipolysis and an accumulation of dysfunctional B1 B cells in the visceral white adipose tissue (vWAT) of old mice. Lifelong deficiency of B cells results in restored non-canonical lipolysis and reductions in pro-inflammatory macrophage populations. Our study suggests that targeting the B cell-macrophage signaling axis may resolve metabolic dysfunction in aged vWAT and attenuate septic severity in older individuals.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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