TY - JOUR
T1 - Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis
AU - Gaddis, Dalia E.
AU - Padgett, Lindsey E.
AU - Wu, Runpei
AU - McSkimming, Chantel
AU - Romines, Veronica
AU - Taylor, Angela M.
AU - McNamara, Coleen A.
AU - Kronenberg, Mitchell
AU - Crotty, Shane
AU - Thomas, Michael J.
AU - Sorci-Thomas, Mary G.
AU - Hedrick, Catherine C.
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-03493-5
DO - 10.1038/s41467-018-03493-5
M3 - Article
C2 - 29545616
AN - SCOPUS:85044288848
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1095
ER -