| First Author | Kim SJ | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 2 | Pages | 823-33 |
| PubMed ID | 23298838 | Mgi Jnum | J:194496 |
| Mgi Id | MGI:5473940 | Doi | 10.1172/JCI64712 |
| Citation | Kim SJ, et al. (2013) Regulation of dendritic cell activation by microRNA let-7c and BLIMP1. J Clin Invest 123(2):823-33 |
| abstractText | Mice with a DC-specific deletion of the transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp1) exhibit a lupus-like phenotype, secondary to enhanced DC production of IL-6. Here we explored further phenotypic changes in Blimp1-deficient DCs, the molecular mechanism underlying these changes, and their relevance to human disease. Blimp1-deficient DCs exhibited elevated expression of MHC II, and exposure to TLR agonists increased secretion of proinflammatory cytokines. This phenotype reflects enhanced expression of the microRNA let-7c, which is regulated by BLIMP1. Let-7c reciprocally inhibited Blimp1 and also blocked LPS-induced suppressor of cytokine signaling-1 (SOCS1) expression, contributing to the proinflammatory phenotype of Blimp1-deficient DCs. DCs from Blimp1 SLE-risk allele carriers exhibited analogous phenotypic changes, including decreased BLIMP1 expression, increased let-7c expression, and increased expression of proinflammatory cytokines. These results suggest that let-7c regulates DC phenotype and confirm the importance of BLIMP1 in maintaining tolerogenic DCs in both mice and humans. |
