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 Dalt, Andrea Annoni, Silvia Gregori, Qingzhong Xiao, Donatella Caruso, Nico Mitro, Alberico L. Catapano, Federica M. Marelli-Berg and Giuseppe D. Norata ()
Additional contact information
Fabrizia Bonacina: Università Degli Studi di Milano
David Coe: Queen Mary University of London
Guosu Wang: Queen Mary University of London
Maria P. Longhi: Queen Mary University of London
Andrea Baragetti: Università Degli Studi di Milano
Annalisa Moregola: Università Degli Studi di Milano
Katia Garlaschelli: Bassini Hospital
Patrizia Uboldi: Università Degli Studi di Milano
Fabio Pellegatta: Bassini Hospital
Liliana Grigore: Bassini Hospital
Lorenzo Dalt: Università Degli Studi di Milano
Andrea Annoni: IRCCS San Raffaele Scientific Institute
Silvia Gregori: IRCCS San Raffaele Scientific Institute
Qingzhong Xiao: Queen Mary University of London
Donatella Caruso: Università Degli Studi di Milano
Nico Mitro: Università Degli Studi di Milano
Alberico L. Catapano: Università Degli Studi di Milano
Federica M. Marelli-Berg: Queen Mary University of London
Giuseppe D. Norata: Università Degli Studi di Milano

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05322-1

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