dc.contributor.author | Chiurchiù, V | en_US |
dc.contributor.author | Leuti, A | en_US |
dc.contributor.author | Dalli, J | en_US |
dc.contributor.author | Jacobsson, A | en_US |
dc.contributor.author | Battistini, L | en_US |
dc.contributor.author | Maccarrone, M | en_US |
dc.contributor.author | Serhan, CN | en_US |
dc.date.accessioned | 2016-11-01T08:58:38Z | |
dc.date.available | 2016-08-24 | en_US |
dc.date.issued | 2016-08-24 | en_US |
dc.date.submitted | 2016-10-21T12:39:40.241Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/16182 | |
dc.description.abstract | Resolution of inflammation is a finely regulated process mediated by specialized proresolving lipid mediators (SPMs), including docosahexaenoic acid (DHA)-derived resolvins and maresins. The immunomodulatory role of SPMs in adaptive immune cells is of interest. We report that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulate adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduce cytokine production by activated CD8(+) T cells and CD4(+) T helper 1 (TH1) and TH17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate. Moreover, these SPMs prevented naïve CD4(+) T cell differentiation into TH1 and TH17 by down-regulating their signature transcription factors, T-bet and Rorc, in a mechanism mediated by the GPR32 and ALX/FPR2 receptors; they concomitantly enhanced de novo generation and function of Foxp3(+) regulatory T (Treg) cells via the GPR32 receptor. These results were also supported in vivo in a mouse deficient for DHA synthesis (Elovl2(-/-)) that showed an increase in TH1/TH17 cells and a decrease in Treg cells compared to wild-type mice. Additionally, either DHA supplementation in Elovl2(-/-) mice or in vivo administration of resolvin D1 significantly reduced cytokine production upon specific stimulation of T cells. These findings demonstrate actions of specific SPMs on adaptive immunity and provide a new avenue for SPM-based approaches to modulate chronic inflammation. | en_US |
dc.description.sponsorship | This work was supported by Fondazione Italiana Sclerosi Multipla (FISM) to V.C.
(grant 2015/R/8) and in part by National Institutes of Health (P01095467 and
GM38765) to C.N.S, by Ministero dell’Istruzione, dell’Università e della Ricerca
(PRIN grant 2010–2011) to M.M., and by Ministero della Salute (RF-2011-
02346771) and FISM (grant 2013/R/2) to L.B. | en_US |
dc.format.extent | 353ra111 - ? | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Sci Transl Med | en_US |
dc.rights | This is the author’s version of the work. It is posted here by permission of the AAAS for personaluse, not for redistribution. The definitive version was published in Science Translational Medicine on 24 Aug 2016: Vol. 8, Issue 353, pp. 353ra111, DOI: 10.1126/scitranslmed.aaf7483 | |
dc.subject | Acetyltransferases | en_US |
dc.subject | Adaptive Immunity | en_US |
dc.subject | Adaptor Proteins, Signal Transducing | en_US |
dc.subject | Animals | en_US |
dc.subject | Cell Differentiation | en_US |
dc.subject | Docosahexaenoic Acids | en_US |
dc.subject | Fatty Acid Elongases | en_US |
dc.subject | Humans | en_US |
dc.subject | Inflammation | en_US |
dc.subject | Inflammation Mediators | en_US |
dc.subject | Interleukin-2 | en_US |
dc.subject | Lipid Metabolism | en_US |
dc.subject | Lymphocyte Activation | en_US |
dc.subject | Mice | en_US |
dc.subject | Mice, Knockout | en_US |
dc.subject | Receptors, Formyl Peptide | en_US |
dc.subject | Receptors, G-Protein-Coupled | en_US |
dc.subject | Receptors, Lipoxin | en_US |
dc.subject | T-Lymphocyte Subsets | en_US |
dc.subject | T-Lymphocytes | en_US |
dc.title | Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses. | en_US |
dc.type | Article | |
dc.rights.holder | (c) The Authors, 2016 | |
dc.identifier.doi | 10.1126/scitranslmed.aaf7483 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/27559094 | en_US |
pubs.issue | 353 | en_US |
pubs.notes | No embargo | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 8 | en_US |
dcterms.dateAccepted | 2016-07-22 | en_US |