Transcription factor Fli-1 impacts the expression of CXCL13 and regulates immune cell infiltration into the kidney in MRL/lpr mouse
In: Lupus Science and Medicine, Jg. 10 (2023), Heft 1
Online
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Zugriff:
Objective Friend leukaemia virus integration 1 (Fli-1) regulates chemokine/cytokine expression and thus plays an important role in the development of lupus nephritis. Chemokine CXC ligand 13 (CXCL13) is a chemokine that promotes the formation of ectopic lymphoid structures and has been reported to be associated with the pathogenesis of lupus nephritis. The relationship between Fli-1 and CXCL13 is unknown. This study aims to elucidate whether Fli-1 impacts CXCL13 expression and contributes to the progression of lupus-like nephritis in adult MRL/lpr mouse.Methods Serum CXCL13 levels were measured in adult wild-type (WT) MRL/lpr mice and Fli-1 heterozygote knockout (Fli-1+/−) MRL/lpr mice (4 months old or older) using ELISA. Renal mRNA expression (CXCL13 and related molecules) was measured using real-time PCR method. Kidneys were removed, stained and evaluated using a pathology scoring system. The grade of CXCL13 or CXC-chemokine receptor type 5 (CXCR5)-positive immune cell infiltration into the kidney was evaluated using immunostaining with anti-CXCL13 or anti-CXCR5 antibodies. We also used immunofluorescence staining with CXCL13- and CD11b-specific antibodies to detect the infiltration of CXCL13/CD11b double-positive immune cells.Results Serum CXCL13 levels in Fli-1+/− MRL/lpr mice were significantly lower than that in WT MRL/lpr mice (545.5 and 960.5 pg/mL, p=0.02). Renal expression of CXCL13 mRNA and SRY-related HMG box4 (Sox4) (an important factor for B-cell development) levels were significantly lower in Fli-1+/− MRL/lpr mice. Renal histology scores in WT MRL/lpr mice revealed significantly increased glomerular inflammation. Despite similar interstitial immune cell infiltration into the kidney, the number of CXCL13- and CXCR5-positive cells was significantly lower in Fli-1+/− MRL/lpr mice than in WT mice. Furthermore, immunofluorescence staining revealed that Fli-1+/-MRL/lpr mice had significantly fewer CXCL13/CD11b double-positive immune cells.Conclusion Fli-1 regulates renal Sox4 mRNA expression and infiltration of CXCR5-positive cells as well as CXCL13/CD11b double-positive immune cells into the kidney, which affects CXCL13 expression and lupus-like nephritis.
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Transcription factor Fli-1 impacts the expression of CXCL13 and regulates immune cell infiltration into the kidney in MRL/lpr mouse
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Autor/in / Beteiligte Person: | Yoshida, Shuhei ; Saito, Kenji ; Fujita, Yuya ; Migita, Kiyoshi ; Matsuoka, Naoki ; Sato, Shuzo ; Xian K Zhang ; Sumichika, Yuya ; Matsumoto, Haruki ; Temmoku, Jumpei ; Asano, Tomoyuki |
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Zeitschrift: | Lupus Science and Medicine, Jg. 10 (2023), Heft 1 |
Veröffentlichung: | BMJ Publishing Group, 2023 |
Medientyp: | academicJournal |
ISSN: | 2053-8790 (print) |
DOI: | 10.1136/lupus-2022-000870 |
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