Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation

Fabrizia Bonacina, David Coe, Guosu Wang, Maria P. Longhi, Andrea Baragetti, Annalisa Moregola, Katia Garlaschelli, Patrizia Uboldi, Fabio Pellegatta, Liliana Grigore, Lorenzo Da Dalt, Andrea Annoni, Silvia Gregori, Qingzhong Xiao, Donatella Caruso, Nico Mitro, Alberico L. Catapano, Federica M. Marelli-Berg, Giuseppe D. Norata

Research output: Contribution to journalArticle

Abstract

Cholesterol homeostasis has a pivotal function in regulating immune cells. Here we show that apolipoprotein E (apoE) deficiency leads to the accumulation of cholesterol in the cell membrane of dendritic cells (DC), resulting in enhanced MHC-II-dependent antigen presentation and CD4+ T-cell activation. Results from WT and apoE KO bone marrow chimera suggest that apoE from cells of hematopoietic origin has immunomodulatory functions, regardless of the onset of hypercholesterolemia. Humans expressing apoE4 isoform (ε4/3–ε4/4) have increased circulating levels of activated T cells compared to those expressing WT apoE3 (ε3/3) or apoE2 isoform (ε2/3–ε2/2). This increase is caused by enhanced antigen-presentation by apoE4-expressing DCs, and is reversed when these DCs are incubated with serum containing WT apoE3. In summary, our study identifies myeloid-produced apoE as a key physiological modulator of DC antigen presentation function, paving the way for further explorations of apoE as a tool to improve the management of immune diseases.

Original languageEnglish
Article number3083
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Bonacina, F., Coe, D., Wang, G., Longhi, M. P., Baragetti, A., Moregola, A., Garlaschelli, K., Uboldi, P., Pellegatta, F., Grigore, L., Da Dalt, L., Annoni, A., Gregori, S., Xiao, Q., Caruso, D., Mitro, N., Catapano, A. L., Marelli-Berg, F. M., & Norata, G. D. (2018). Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation. Nature Communications, 9(1), [3083]. https://doi.org/10.1038/s41467-018-05322-1