2. Academic Validation
  3. The miR-17∼92 miRNAs promote plasma cell differentiation by suppressing SOCS3-mediated NIK degradation

The miR-17∼92 miRNAs promote plasma cell differentiation by suppressing SOCS3-mediated NIK degradation

  • Cell Rep. 2023 Aug 13;42(8):112968. doi: 10.1016/j.celrep.2023.112968.
Jun Xie 1,  Ying Du 1,  Dewang Liu 1,  Jianfeng Wu 1,  Kang Yang 1,  Xiaoyu He 1,  Jiayi Zhao 1,  Peicheng Hong 1,  Kunyu Liao 1,  Huanrong Zhang 1,  Yazhen Hong 1,  John R Teijaro 2,  Seung Goo Kang 3,  Changchun Xiao 4,  Wen-Hsien Liu 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
  • 2 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • 3 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA; Division of Biomedical Convergence/Institute of Bioscience and Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: sgkang@kangwon.ac.kr.
  • 4 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: cxiao@scripps.edu.
  • 5 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: whliu@xmu.edu.cn.
PMID: 37578862 DOI: 10.1016/j.celrep.2023.112968
Abstract

The miR-17∼92 family MicroRNAs (miRNAs) play a key role in germinal center (GC) reaction through promoting T follicular helper (TFH) cell differentiation. It remains unclear whether they also have intrinsic functions in B cell differentiation and function. Here we show that mice with B cell-specific deletion of the miR-17∼92 family exhibit impaired GC reaction, plasma cell differentiation, and antibody production in response to protein antigen immunization and chronic viral Infection. Employing CRISPR-mediated functional screening, we identify Socs3 as a key functional target of miR-17∼92 in regulating plasma cell differentiation. Mechanistically, SOCS3, whose expression is elevated in miR-17∼92 family-deficient B cells, interacts with NIK and promotes its ubiquitination and degradation, thereby impairing NF-κB signaling and plasma cell differentiation. This moderate increase in SOCS3 expression has little effect on IL-21-STAT3 signaling. Our study demonstrates differential sensitivity of two key signaling pathways to alterations in the protein level of an miRNA target gene.

Keywords

CP: Immunology; CP: Molecular biology.

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