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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 | Catherine C Hedrick
Nature communications | 2018

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.

Pubmed ID: 29545616

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL127649
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR027366
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL136275
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI072543
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI089624
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL055798
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI125179
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL112276

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