| First Author | Schmidtke L | Year | 2021 |
| Journal | Cells | Volume | 10 |
| Issue | 11 | PubMed ID | 34831390 |
| Mgi Jnum | J:319936 | Mgi Id | MGI:6827567 |
| Doi | 10.3390/cells10113167 | Citation | Schmidtke L, et al. (2021) Knockout of the KH-Type Splicing Regulatory Protein Drives Glomerulonephritis in MRL-Fas(lpr) Mice. Cells 10(11) |
| abstractText | KH-type splicing regulatory protein (KSRP) is an RNA-binding protein that promotes mRNA decay and thereby negatively regulates cytokine expression at the post-transcriptional level. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated cytokine expression causing multiple organ manifestations; MRL-Fas(lpr) mice are an established mouse model to study lupus disease pathogenesis. To investigate the impact of KSRP on lupus disease progression, we generated KSRP-deficient MRL-Fas(lpr) mice (MRL-Fas(lpr)/KSRP(-/-) mice). In line with the predicted role of KSRP as a negative regulator of cytokine expression, lupus nephritis was augmented in MRL-Fas(lpr)/KSRP(-/-) mice. Increased infiltration of immune cells, especially of IFN-gamma producing T cells and macrophages, driven by enhanced expression of T cell-attracting chemokines and adhesion molecules, seems to be responsible for worsened kidney morphology. Reduced expression of the anti-inflammatory interleukin-1 receptor antagonist may be another reason for severe inflammation. The increase of FoxP3(+) T cells detected in the kidney seems unable to dampen the massive kidney inflammation. Interestingly, lymphadenopathy was reduced in MRL-Fas(lpr)/KSRP(-/-) mice. Altogether, KSRP appears to have a complex role in immune regulation; however, it is clearly able to ameliorate lupus nephritis. |
