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Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b
Reciprocal interactions between B and follicular T helper (Tfh) cells orchestrate the germinal center (GC) reaction, a hallmark of humoral immunity. Abnormal GC responses could lead to the production of pathogenic autoantibodies and the development of autoimmunity. Here we show that miR-146a control...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048122/ https://www.ncbi.nlm.nih.gov/pubmed/30013024 http://dx.doi.org/10.1038/s41467-018-05196-3 |
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author | Cho, Sunglim Lee, Hyang-Mi Yu, I-Shing Choi, Youn Soo Huang, Hsi-Yuan Hashemifar, Somaye Sadat Lin, Ling-Li Chen, Mei-Chi Afanasiev, Nikita D. Khan, Aly Azeem Lin, Shu-Wha Rudensky, Alexander Y. Crotty, Shane Lu, Li-Fan |
author_facet | Cho, Sunglim Lee, Hyang-Mi Yu, I-Shing Choi, Youn Soo Huang, Hsi-Yuan Hashemifar, Somaye Sadat Lin, Ling-Li Chen, Mei-Chi Afanasiev, Nikita D. Khan, Aly Azeem Lin, Shu-Wha Rudensky, Alexander Y. Crotty, Shane Lu, Li-Fan |
author_sort | Cho, Sunglim |
collection | PubMed |
description | Reciprocal interactions between B and follicular T helper (Tfh) cells orchestrate the germinal center (GC) reaction, a hallmark of humoral immunity. Abnormal GC responses could lead to the production of pathogenic autoantibodies and the development of autoimmunity. Here we show that miR-146a controls GC responses by targeting multiple CD40 signaling pathway components in B cells; by contrast, loss of miR-146a in T cells does not alter humoral responses. However, specific deletion of both miR-146a and its paralog, miR-146b, in T cells increases Tfh cell numbers and enhanced GC reactions. Thus, our data reveal differential cell-intrinsic regulations of GC B and Tfh cells by miR-146a and miR-146b. Together, members of the miR-146 family serve as crucial molecular brakes to coordinately control GC reactions to generate protective humoral responses without eliciting unwanted autoimmunity. |
format | Online Article Text |
id | pubmed-6048122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60481222018-07-18 Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b Cho, Sunglim Lee, Hyang-Mi Yu, I-Shing Choi, Youn Soo Huang, Hsi-Yuan Hashemifar, Somaye Sadat Lin, Ling-Li Chen, Mei-Chi Afanasiev, Nikita D. Khan, Aly Azeem Lin, Shu-Wha Rudensky, Alexander Y. Crotty, Shane Lu, Li-Fan Nat Commun Article Reciprocal interactions between B and follicular T helper (Tfh) cells orchestrate the germinal center (GC) reaction, a hallmark of humoral immunity. Abnormal GC responses could lead to the production of pathogenic autoantibodies and the development of autoimmunity. Here we show that miR-146a controls GC responses by targeting multiple CD40 signaling pathway components in B cells; by contrast, loss of miR-146a in T cells does not alter humoral responses. However, specific deletion of both miR-146a and its paralog, miR-146b, in T cells increases Tfh cell numbers and enhanced GC reactions. Thus, our data reveal differential cell-intrinsic regulations of GC B and Tfh cells by miR-146a and miR-146b. Together, members of the miR-146 family serve as crucial molecular brakes to coordinately control GC reactions to generate protective humoral responses without eliciting unwanted autoimmunity. Nature Publishing Group UK 2018-07-16 /pmc/articles/PMC6048122/ /pubmed/30013024 http://dx.doi.org/10.1038/s41467-018-05196-3 Text en © 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/. |
spellingShingle | Article Cho, Sunglim Lee, Hyang-Mi Yu, I-Shing Choi, Youn Soo Huang, Hsi-Yuan Hashemifar, Somaye Sadat Lin, Ling-Li Chen, Mei-Chi Afanasiev, Nikita D. Khan, Aly Azeem Lin, Shu-Wha Rudensky, Alexander Y. Crotty, Shane Lu, Li-Fan Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b |
title | Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b |
title_full | Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b |
title_fullStr | Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b |
title_full_unstemmed | Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b |
title_short | Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b |
title_sort | differential cell-intrinsic regulations of germinal center b and t cells by mir-146a and mir-146b |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048122/ https://www.ncbi.nlm.nih.gov/pubmed/30013024 http://dx.doi.org/10.1038/s41467-018-05196-3 |
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