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Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis

Author

Listed:
  • Dalia E. Gaddis

    (La Jolla Institute for Allergy and Immunology)

  • Lindsey E. Padgett

    (La Jolla Institute for Allergy and Immunology)

  • Runpei Wu

    (La Jolla Institute for Allergy and Immunology)

  • Chantel McSkimming

    (University of Virginia)

  • Veronica Romines

    (La Jolla Institute for Allergy and Immunology)

  • Angela M. Taylor

    (University of Virginia)

  • Coleen A. McNamara

    (University of Virginia)

  • Mitchell Kronenberg

    (La Jolla Institute for Allergy and Immunology)

  • Shane Crotty

    (La Jolla Institute for Allergy and Immunology
    UCSD School of Medicine)

  • Michael J. Thomas

    (Medical College of Wisconsin)

  • Mary G. Sorci-Thomas

    (Medical College of Wisconsin
    Medical College of Wisconsin)

  • Catherine C. Hedrick

    (La Jolla Institute for Allergy and Immunology)

Abstract

Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here we show that during atherogenesis Treg cells lose Foxp3 expression and their immunosuppressive function, leading to the conversion of a fraction of these cells into T follicular helper (Tfh) cells. We show that Tfh cells are pro-atherogenic and that their depletion reduces atherosclerosis. Mechanistically, the conversion of Treg cells to Tfh cells correlates with reduced expression of IL-2Rα and pSTAT5 levels and increased expression of IL-6Rα. In vitro, incubation of naive T cells with oxLDL prevents their differentiation into Treg cells. Furthermore, injection of lipid-free Apolipoprotein AI (ApoAI) into ApoE−/− mice reduces intracellular cholesterol levels in Treg cells and prevents their conversion into Tfh cells. Together our results suggest that ApoAI, the main protein in high-density lipoprotein particles, modulates the cellular fate of Treg cells and thus influences the immune response during atherosclerosis.

Suggested Citation

  • Dalia E. Gaddis & Lindsey E. Padgett & Runpei Wu & Chantel McSkimming & Veronica Romines & Angela M. Taylor & Coleen A. McNamara & Mitchell Kronenberg & Shane Crotty & Michael J. Thomas & Mary G. Sorc, 2018. "Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03493-5
    DOI: 10.1038/s41467-018-03493-5
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    Cited by:

    1. Marc Scherlinger & Hao Li & Wenliang Pan & Wei Li & Kohei Karino & Theodoros Vichos & Afroditi Boulougoura & Nobuya Yoshida & Maria G. Tsokos & George C. Tsokos, 2024. "CaMK4 controls follicular helper T cell expansion and function during normal and autoimmune T-dependent B cell responses," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Venetia Bazioti & Anouk M. Rose & Sjors Maassen & Frans Bianchi & Rinse Boer & Benedek Halmos & Deepti Dabral & Emma Guilbaud & Arthur Flohr-Svendsen & Anouk G. Groenen & Alejandro Marmolejo-Garza & M, 2022. "T cell cholesterol efflux suppresses apoptosis and senescence and increases atherosclerosis in middle aged mice," Nature Communications, Nature, vol. 13(1), pages 1-23, December.

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