Knockout of the KH-Type Splicing Regulatory Protein Drives Glomerulonephritis in MRL-Faslpr Mice
| Autor: | Katharina Schrick, Myriam Meineck, Lisa Schmidtke, Hartmut Kleinert, Rudolf Käfer, Julia Weinmann-Menke, Wilfried Roth, Svenja Otten, Sabrina Saurin, Andrea Pautz, Fabian Gather |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Chemokine Mice Inbred MRL lpr QH301-705.5 medicine.medical_treatment Lupus nephritis Biology Kidney Article Immune system systemic lupus erythematosus immune system diseases medicine cytokine Animals CD11a Antigen RNA Messenger KSRP Biology (General) skin and connective tissue diseases Regulation of gene expression Mice Knockout Systemic lupus erythematosus FOXP3 RNA-Binding Proteins Glomerulonephritis General Medicine medicine.disease Mice Inbred C57BL Cytokine Cancer research biology.protein Trans-Activators Female Lymph Nodes Chemokines Biomarkers glomerulonephritis post-transcriptional regulation |
| Zdroj: | Cells Volume 10 Issue 11 Cells, Vol 10, Iss 3167, p 3167 (2021) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10113167 |
| Popis: | 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-Faslpr 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-Faslpr mice (MRL-Faslpr/KSRP−/− mice). In line with the predicted role of KSRP as a negative regulator of cytokine expression, lupus nephritis was augmented in MRL-Faslpr/KSRP−/− mice. Increased infiltration of immune cells, especially of IFN-γ 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-Faslpr/KSRP−/− mice. Altogether, KSRP appears to have a complex role in immune regulation however, it is clearly able to ameliorate lupus nephritis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |