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, and Vinuesa, Carola G. (2015) MicroRNA-146a regulates ICOS–ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres. Nature Communications, 6. 6436. pp. 1-14.
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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 ddition,miR-146a deficiency leads to increased ICOSL expression on GC B cells and antigenpresentingcells. 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.
| Item ID: | 37821 |
|---|---|
| Item Type: | Article (Research - C1) |
| ISSN: | 2041-1723 |
| Additional Information: | This 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/ |
| Funders: | National Health and Medical Research Council of Australia (NHMRC) |
| Date Deposited: | 19 Mar 2015 03:55 |
| FoR Codes: | 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110706 Immunogenetics (incl Genetic Immunology) @ 100% |
| SEO Codes: | 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100% |
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