Transcription factor Fli-1 impacts the expression of CXCL13 and regulates immune cell infiltration into the kidney in MRL/lpr mouse.
In: Lupus science & medicine, Jg. 10 (2023-04-01), Heft 1
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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.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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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: | Sato, S ; Zhang, XK ; Matsuoka, N ; Sumichika, Y ; Saito, K ; Yoshida, S ; Matsumoto, H ; Temmoku, J ; Fujita, Y ; Asano, T ; Migita, K |
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Zeitschrift: | Lupus science & medicine, Jg. 10 (2023-04-01), Heft 1 |
Veröffentlichung: | London : BMJ, [2014]-, 2023 |
Medientyp: | academicJournal |
ISSN: | 2053-8790 (print) |
DOI: | 10.1136/lupus-2022-000870 |
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