Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis.
Dalia E GaddisLindsey E PadgettRunpei WuChantel McSkimmingVeronica RominesAngela M TaylorColeen A McNamaraMitchell KronenbergShane CrottyMichael J ThomasMary G Sorci-ThomasCatherine C HedrickPublished in: 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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- immune response
- poor prognosis
- cardiovascular disease
- oxidative stress
- deep learning
- anti inflammatory
- dendritic cells
- metabolic syndrome
- high density
- adipose tissue
- binding protein
- small molecule
- mouse model
- long non coding rna
- toll like receptor
- artificial intelligence
- pi k akt
- protein protein
- fatty acid
- antiretroviral therapy
- ultrasound guided