Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses
Number of Authors: 7
2016 (English)In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 8, no 353, 353ra111Article in journal (Refereed) Published
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 (T(H)1) and T(H)17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate. Moreover, these SPMs prevented naive CD4(+) T cell differentiation into T(H)1 and T(H)17 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 (T-reg) 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 T(H)1/T(H)17 cells and a decrease in T-reg 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.
Place, publisher, year, edition, pages
2016. Vol. 8, no 353, 353ra111
Biological Sciences Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:su:diva-135103DOI: 10.1126/scitranslmed.aaf7483ISI: 000384014200001OAI: oai:DiVA.org:su-135103DiVA: diva2:1048200