| First Author | Xie J | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 8 | Pages | 112968 |
| PubMed ID | 37578862 | Mgi Jnum | J:340114 |
| Mgi Id | MGI:7524644 | Doi | 10.1016/j.celrep.2023.112968 |
| Citation | Xie J, et al. (2023) The miR-17 approximately 92 miRNAs promote plasma cell differentiation by suppressing SOCS3-mediated NIK degradation. Cell Rep 42(8):112968 |
| abstractText | The miR-17 approximately 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 approximately 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 approximately 92 in regulating plasma cell differentiation. Mechanistically, SOCS3, whose expression is elevated in miR-17 approximately 92 family-deficient B cells, interacts with NIK and promotes its ubiquitination and degradation, thereby impairing NF-kappaB 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. |
