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

作者：Xie, Jun; Du, Ying; Liu, Dewang; Wu, Jianfeng; Yang, Kang; He, Xiaoyu; Zhao, Jiayi; Hong, Peicheng; Liao, Kunyu; Zhang, Huanrong; Hong, Yazhen; Teijaro, John R.; Kang, Seung Goo^*; Xiao, Changchun^*; Liu, Wen-Hsien^*

来源：Cell Reports, 2023, 42(8): 112968.

DOI：10.1016/j.celrep.2023.112968

• GERMINAL CENTER B
• NF-KAPPA-B
• GENE-EXPRESSION
• BLIMP-1
• GENERATION
• MICRORNA-155
• ACTIVATION
• DELETION
• PATHWAY
• PAX5

The miR-17 similar to 92 family microRNAs (miRNAs) play a key role in germinal center (GC) reaction through promoting T follicular helper (T-FH) 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 similar to 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 similar to 92 in regulating plasma cell differentiation. Mechanistically, SOCS3, whose expression is elevated in miR-17 similar to 92 family-deficient B cells, interacts with NIK and promotes its ubiquitination and degradation, thereby impairing NF-kappa B 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.

• 单位
  厦门大学; 细胞应激生物学国家重点实验室