Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29545616.
- Also identified by DOI 10.1038/s41467-018-03493-5 and PMC identifier 5854619.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-/-</sup> 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.
Medical subject headings
- Apolipoprotein A-I
- Atherosclerosis
- Cell Differentiation
- T-Lymphocytes, Helper-Inducer
- T-Lymphocytes, Regulatory