Oleinika, K;
Rosser, EC;
Matei, DE;
Nistala, K;
Bosma, A;
Drozdov, I;
Mauri, C;
(2018)
CD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells.
Nature Communications
, 9
, Article 684. 10.1038/s41467-018-02911-y.
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Abstract
Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d–lipid presentation by Bregs induces iNKT cells to secrete interferon (IFN)-γ to contribute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive immune responses and ameliorate experimental arthritis. Mice lacking CD1d-expressing B cells develop exacerbated disease compared to wild-type mice, and fail to respond to treatment with the prototypical iNKT cell agonist α-galactosylceramide. The absence of lipid presentation by B cells alters iNKT cell activation with disruption of metabolism regulation and cytokine responses. Thus, we identify a mechanism by which Bregs restrain excessive inflammation via lipid presentation.
| Type: | Article |
|---|---|
| Title: | CD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-018-02911-y |
| Publisher version: | http://doi.org/10.1038/s41467-018-02911-y |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. |
| Keywords: | Autoimmunity, B cells, Cellular immunity, NKT cells |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10045973 |
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