Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis. Nat Commun 2018 Mar 15;9(1):1095
Date
03/17/2018Pubmed ID
29545616Pubmed Central ID
PMC5854619DOI
10.1038/s41467-018-03493-5Scopus ID
2-s2.0-85044288848 (requires institutional sign-in at Scopus site) 116 CitationsAbstract
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.
Author List
Gaddis DE, Padgett LE, Wu R, McSkimming C, Romines V, Taylor AM, McNamara CA, Kronenberg M, Crotty S, Thomas MJ, Sorci-Thomas MG, Hedrick CCAuthors
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of WisconsinMichael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsApolipoprotein A-I
Atherosclerosis
Cell Differentiation
Female
Humans
Interleukin-2 Receptor alpha Subunit
Male
Mice
Mice, Knockout
Receptors, Interleukin-6
STAT5 Transcription Factor
T-Lymphocytes, Helper-Inducer
T-Lymphocytes, Regulatory
