Skip navigation
Skip navigation
The system will be down for maintenance between 8:00 and 8:15am on Thursday 13, December 2018

MicroRNA-146a regulates ICOS–ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres

Pratama, Alvin; Srivastava, Monika; Williams, Naomi J.; Papa, Ilenia; Lee, Sau K.; Dinh, Xuyen T.; Hutloff, Andreas; Jordan, Margaret A.; Zhao, Jimmy L.; Casellas, Rafael; Athanasopoulos, Vicki; Vinuesa, Carola

Description

Tight control of T follicular helper (Tfh) cells is required for optimal maturation of the germinal centre (GC) response. The molecular mechanisms controlling Tfh-cell differentiation remain incompletely understood. Here we show that microRNA-146a (miR-146a) is highly expressed in Tfh cells and peak miR-146a expression marks the decline of the Tfh response after immunization. Loss of miR-146a causes cell-intrinsic accumulation of Tfh and GC B cells. MiR-146a represses several Tfh-cell-expressed...[Show more]

dc.contributor.authorPratama, Alvin
dc.contributor.authorSrivastava, Monika
dc.contributor.authorWilliams, Naomi J.
dc.contributor.authorPapa, Ilenia
dc.contributor.authorLee, Sau K.
dc.contributor.authorDinh, Xuyen T.
dc.contributor.authorHutloff, Andreas
dc.contributor.authorJordan, Margaret A.
dc.contributor.authorZhao, Jimmy L.
dc.contributor.authorCasellas, Rafael
dc.contributor.authorAthanasopoulos, Vicki
dc.contributor.authorVinuesa, Carola
dc.date.accessioned2015-06-04T02:48:40Z
dc.date.available2015-06-04T02:48:40Z
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/1885/13779
dc.description.abstractTight control of T follicular helper (Tfh) cells is required for optimal maturation of the germinal centre (GC) response. The molecular mechanisms controlling Tfh-cell differentiation remain incompletely understood. Here we show that microRNA-146a (miR-146a) is highly expressed in Tfh cells and peak miR-146a expression marks the decline of the Tfh response after immunization. Loss of miR-146a causes cell-intrinsic accumulation of Tfh and GC B cells. MiR-146a represses several Tfh-cell-expressed messenger RNAs, and of these, ICOS is the most strongly cell autonomously upregulated target in miR-146a-deficient T cells. In addition, miR-146a deficiency leads to increased ICOSL expression on GC B cells and antigen-presenting cells. Partial blockade of ICOS signalling, either by injections of low dose of ICOSL blocking antibody or by halving the gene dose of Icos in miR-146a-deficient T cells, prevents the Tfh and GC B-cell accumulation. Collectively, miR-146a emerges as a post-transcriptional brake to limit Tfh cells and GC responses.
dc.description.sponsorshipThis work was funded by the National Health and Medical Research Council (NHMRC) program and project grants and Elizabeth Blackburn Fellowship to C.G.V., International Postgraduate Research Scholarship to A.P., NHMRC/MSRA Betty Cuthbert Fellowship to M.A.J., National Research Service Award F30HL110691 and UCLA/Caltech Medical Scientist Training Program to J.L.Z.
dc.format14 pages
dc.publisherNature Publishing Group
dc.rights© 2015 Macmillan Publishers Limited
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.sourceNature Communications
dc.titleMicroRNA-146a regulates ICOS–ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres
dc.typeJournal article
local.identifier.citationvolume6
dcterms.dateAccepted2015-01-28
dc.date.issued2015-03-06
local.identifier.absfor110799 - Immunology not elsewhere classified
local.identifier.absfor110700 - IMMUNOLOGY
local.identifier.absfor110703 - Autoimmunity
local.identifier.ariespublicationa383154xPUB2413
local.publisher.urlhttp://www.nature.com/
local.type.statusPublished Version
local.contributor.affiliationPratama, A., John Curtin School of Medical Research, The Australian National University
local.contributor.affiliationSrivastava, M., John Curtin School of Medical Research, The Australian National University
local.contributor.affiliationWilliams, N. J., John Curtin School of Medical Research, The Australian National University
local.contributor.affiliationPapa, I., John Curtin School of Medical Research, The Australian National University
local.contributor.affiliationLee, S. K., John Curtin School of Medical Research, The Australian National University
local.contributor.affiliationAthanasopoulos, V., John Curtin School of Medical Research, The Australian National University
local.contributor.affiliationVinuesa, C. G., John Curtin School of Medical Research, The Australian National University
local.identifier.essn2041-1723
local.bibliographicCitation.startpage6436
local.bibliographicCitation.lastpage14
local.identifier.doi10.1038/ncomms7436
local.identifier.absseo920108 - Immune System and Allergy
dc.date.updated2015-12-11T07:24:35Z
local.identifier.scopusID2-s2.0-84923365460
CollectionsANU Research Publications

Download

File Description SizeFormat Image
Pratama et al MicroRNA-146a Regulates ICOS-ICOSL 2015.pdf2.65 MBAdobe PDFThumbnail


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  27 November 2018/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator