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

Nature Communications
Alvin PratamaCarola G Vinuesa

Abstract

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 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.

References

Mar 1, 1996·The Journal of Experimental Medicine·J ZhaoL H Glimcher
Dec 23, 1998·European Journal of Immunology·J R TumangH C Liou
Jan 5, 2000·Nature·S K YoshinagaG Senaldi
Aug 10, 2004·Nature Immunology·Christopher D C AllenJason G Cyster
Oct 21, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Katsutoshi OzakiWarren J Leonard
Sep 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lukas BossallerKlaus Warnatz
Sep 26, 2007·Nature Immunology·Alexander LinkSanjiv A Luther
Apr 3, 2008·Arthritis and Rheumatism·Joanna StanczykDiego Kyburz
Apr 29, 2008·Arthritis and Rheumatism·Tomoyuki NakasaHiroshi Asahara
Jun 24, 2008·Nature Cell Biology·Catherine LabbayeCesare Peschle
Sep 2, 2008·Arthritis Research & Therapy·Kaleb M PauleyEdward Kl Chan
Nov 5, 2008·The Journal of Experimental Medicine·Jared M OdegardJoe Craft
Feb 18, 2009·The Journal of Experimental Medicine·Michelle A LintermanCarola G Vinuesa
Mar 3, 2009·Nature Immunology·Nicolas FazilleauMichael G McHeyzer-Williams
Jul 25, 2009·Science·Roza I NurievaChen Dong
Jul 8, 2010·Immunity·Stefan KuchenRafael Casellas
Jul 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guobing ChenM Frances Shannon
Oct 19, 2010·The Journal of Rheumatology·Gang WangCheuk-Chun Szeto
Jan 12, 2011·Annual Review of Immunology·Jennifer L CannonsPamela L Schwartzberg
Feb 15, 2011·Annual Review of Immunology·Shane Crotty
Mar 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Margaret A JordanAlan G Baxter
May 11, 2011·The Journal of Experimental Medicine·Mark P BoldinDavid Baltimore
May 18, 2011·The Journal of Experimental Medicine·Tanja A SchwickertMichel C Nussenzweig
May 18, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jimmy L ZhaoDavid Baltimore
Jul 7, 2011·Molecular and Cellular Biology·Jie MeiChun-Li Zhang
Jul 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Hongbo HuShao-Cong Sun
Jul 26, 2011·Nature Medicine·Michelle A LintermanCarola G Vinuesa
Oct 11, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ivonne WollenbergLuis Graca
May 1, 2012·Cell Reports·Martin EtzrodtMikael J Pittet
May 3, 2012·Nature Reviews. Rheumatology·Joseph E Craft

❮ Previous
Next ❯

Citations

Feb 5, 2016·Wiley Interdisciplinary Reviews. RNA·Andreas SchlundtMichael Sattler
Mar 5, 2016·Cellular and Molecular Life Sciences : CMLS·Lucien P Garo, Gopal Murugaiyan
Dec 18, 2015·Genes and Immunity·J S Schaefer, J R Klein
Oct 4, 2015·Current Opinion in Immunology·Simon H JiangCarola G Vinuesa
Apr 14, 2016·Trends in Immunology·Julia Maul, Dirk Baumjohann
Jun 21, 2015·Trends in Immunology·Peter T Sage, Arlene H Sharpe
Apr 10, 2016·European Journal of Immunology·Vicki AthanasopoulosCarola G Vinuesa
Feb 26, 2016·Annual Review of Immunology·Carola G VinuesaIan C M MacLennan
Aug 3, 2016·The Journal of Experimental Medicine·Wen-Hsien LiuChangchun Xiao
Aug 5, 2016·Journal of Human Genetics·Shingo IchimiyaTetsuo Himi
Aug 31, 2016·Nature Reviews. Immunology·Hai Qi
Feb 20, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Zijun WangZhihui Wang
Apr 1, 2017·Nature Reviews. Rheumatology·Laurence Morel
Jun 2, 2017·Current Opinion in Rheumatology·Xiong LeNan Shen
Feb 23, 2018·Expert Opinion on Therapeutic Targets·Florent AmatoreDaniel Olive
Jan 6, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joseph C LownikRebecca K Martin
Mar 16, 2019·Immunological Reviews·Julia MaulDirk Baumjohann
Mar 16, 2019·Immunological Reviews·Zurong WanHai Qi
Feb 24, 2015·Nature Communications·Monika SrivastavaCarola G Vinuesa
Nov 19, 2019·Expert Opinion on Biological Therapy·Florent AmatoreDaniel Olive
Aug 18, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joseph C LownikDaniel H Conrad
Aug 16, 2018·Frontiers in Immunology·Dirk Baumjohann, Vigo Heissmeyer
Feb 16, 2019·PLoS Genetics·Marah C RuntschRyan M O'Connell
Jun 24, 2017·The Journal of Experimental Medicine·Antje HeitM Juliana McElrath
Apr 25, 2018·The Journal of Cell Biology·Kai P Hoefig, Vigo Heissmeyer
Nov 10, 2018·Frontiers in Immunology·Haijing WuQianjin Lu
Jun 20, 2020·International Reviews of Immunology·Naeim EhteshamMohammadreza Sharifi
Dec 10, 2016·Frontiers in Immunology·Gajendra M JogdandSatish Devadas
Jun 15, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nanette MitterederGianluca Carlesso
Mar 24, 2016·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Marketa Husakova
Jun 20, 2017·Immunology·Louise M C Webb, Michelle A Linterman
Apr 17, 2018·Non-coding RNA·Ugo TestaCatherine Labbaye
Oct 16, 2018·Frontiers in Immunology·Ana Rodríguez-GalánFrancisco Sánchez-Madrid
Oct 16, 2018·Frontiers in Immunology·Jayendra Kumar KrishnaswamyAdam Williams
Aug 16, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kurt A WongElina I Zuniga
Dec 19, 2019·Frontiers in Immunology·Tingting DingCaihong Wang

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE64833

Methods Mentioned

BETA
PCRs
flow cytometry
density gradient centrifugation
PMA
FCS
Assay
PCR

Software Mentioned

FlowJo
FACSDiva
GeneSpring
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.