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

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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 1095 (03 15 2018) ISSN: 2041-1723 [Electronic] England
• PMID: 29545616 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein A-I
• Interleukin-2 Receptor alpha Subunit
• Receptors, Interleukin-6
• STAT5 Transcription Factor

Topics

• Animals
• Apolipoprotein A-I (genetics, immunology)
• Atherosclerosis (genetics, immunology, physiopathology)
• Cell Differentiation
• Female
• Humans
• Interleukin-2 Receptor alpha Subunit (genetics, immunology)
• Male
• Mice
• Mice, Knockout
• Receptors, Interleukin-6 (genetics, immunology)
• STAT5 Transcription Factor (genetics, immunology)
• T-Lymphocytes, Helper-Inducer (cytology, immunology)
• T-Lymphocytes, Regulatory (cytology, immunology)