Author
Listed:
- Alvin Pratama
(John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, Australian Capital Territory 0200, Australia)
- Monika Srivastava
(John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, Australian Capital Territory 0200, Australia)
- Naomi J. Williams
(John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, Australian Capital Territory 0200, Australia)
- Ilenia Papa
(John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, Australian Capital Territory 0200, Australia)
- Sau K. Lee
(John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, Australian Capital Territory 0200, Australia)
- Xuyen T. Dinh
(Comparative Genomics Centre, James Cook University)
- Andreas Hutloff
(Chronic Immune Reactions Group, German Rheumatism Research Centre Berlin (DRFZ), a Leibniz Institute)
- Margaret A. Jordan
(Comparative Genomics Centre, James Cook University)
- Jimmy L. Zhao
(California Institute of Technology)
- Rafael Casellas
(Genomics and Immunity Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health)
- Vicki Athanasopoulos
(John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, Australian Capital Territory 0200, Australia)
- Carola G. Vinuesa
(John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, Australian Capital Territory 0200, Australia)
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.
Suggested Citation
Alvin Pratama & Monika Srivastava & Naomi J. Williams & Ilenia Papa & Sau K. Lee & Xuyen T. Dinh & Andreas Hutloff & Margaret A. Jordan & Jimmy L. Zhao & Rafael Casellas & Vicki Athanasopoulos & Carol, 2015.
"MicroRNA-146a regulates ICOS–ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres,"
Nature Communications, Nature, vol. 6(1), pages 1-14, May.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7436
DOI: 10.1038/ncomms7436
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