dc.contributor.author | Bonacina, F | en_US |
dc.contributor.author | Coe, D | en_US |
dc.contributor.author | Wang, G | en_US |
dc.contributor.author | Longhi, MP | en_US |
dc.contributor.author | Baragetti, A | en_US |
dc.contributor.author | Moregola, A | en_US |
dc.contributor.author | Garlaschelli, K | en_US |
dc.contributor.author | Uboldi, P | en_US |
dc.contributor.author | Pellegatta, F | en_US |
dc.contributor.author | Grigore, L | en_US |
dc.contributor.author | Da Dalt, L | en_US |
dc.contributor.author | Annoni, A | en_US |
dc.contributor.author | Gregori, S | en_US |
dc.contributor.author | Xiao, Q | en_US |
dc.contributor.author | Caruso, D | en_US |
dc.contributor.author | Mitro, N | en_US |
dc.contributor.author | Catapano, AL | en_US |
dc.contributor.author | Marelli-Berg, FM | en_US |
dc.contributor.author | Norata, GD | en_US |
dc.date.accessioned | 2018-08-24T15:28:27Z | |
dc.date.available | 2018-06-24 | en_US |
dc.date.issued | 2018-08-06 | en_US |
dc.date.submitted | 2018-08-16T08:51:36.621Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/43824 | |
dc.description.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. | en_US |
dc.description.sponsorship | . The work of the
authors is supported by: Fondazione Cariplo 2015-0524 and 2015-0564 (A.L.C.) and
2016-0852 (G.D.N.); H2020 REPROGRAM PHC-03-2015/667837-2 (A.L.C.); Telethon
Foundation (GGP13002) (G.D.N.), Ministero della Salute GR-2011-02346974 (G.D.N.)
and GR-2013-02355011 (F.B.); Aspire Cardiovascular Grant 2016-WI218287 (G.D.N.).
F.M.M.-B. is a recipient of the British Heart Foundation Chair of Cardiovascular
Immunology (CH/15/2/32064). | en_US |
dc.format.extent | 3083 - ? | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Nat Commun | en_US |
dc.rights | CC BY | |
dc.subject | Animals | en_US |
dc.subject | Antigen Presentation | en_US |
dc.subject | Apolipoprotein E4 | en_US |
dc.subject | Apolipoproteins E | en_US |
dc.subject | Bone Marrow Cells | en_US |
dc.subject | Cell Differentiation | en_US |
dc.subject | Cell Movement | en_US |
dc.subject | Cholesterol | en_US |
dc.subject | Dendritic Cells | en_US |
dc.subject | Fatty Acids | en_US |
dc.subject | Female | en_US |
dc.subject | Hematopoietic Stem Cells | en_US |
dc.subject | Histocompatibility Antigens Class II | en_US |
dc.subject | Humans | en_US |
dc.subject | Hypercholesterolemia | en_US |
dc.subject | Lymphocyte Activation | en_US |
dc.subject | Major Histocompatibility Complex | en_US |
dc.subject | Male | en_US |
dc.subject | Mice | en_US |
dc.subject | Mice, Inbred BALB C | en_US |
dc.subject | Mice, Inbred C57BL | en_US |
dc.subject | Mice, Knockout | en_US |
dc.subject | Myeloid Cells | en_US |
dc.subject | Oxysterols | en_US |
dc.subject | Phospholipids | en_US |
dc.subject | T-Lymphocytes | en_US |
dc.title | Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1038/s41467-018-05322-1 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30082772 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | No embargo | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 9 | en_US |
dcterms.dateAccepted | 2018-06-24 | en_US |