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

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. Sorci-Thomas and Catherine C. Hedrick ()
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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
Michael J. Thomas: Medical College of Wisconsin
Mary G. Sorci-Thomas: Medical College of Wisconsin
Catherine C. Hedrick: La Jolla Institute for Allergy and Immunology

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03493-5

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