RT Journal Article
SR Electronic
T1 Transcription factor Fli-1 impacts the expression of CXCL13 and regulates immune cell infiltration into the kidney in MRL/lpr mouse
JF Lupus Science & Medicine
JO Lupus Sci Med
FD Lupus Foundation of America
SP e000870
DO 10.1136/lupus-2022-000870
VO 10
IS 1
A1 Shuzo Sato
A1 Xian K Zhang
A1 Naoki Matsuoka
A1 Yuya Sumichika
A1 Kenji Saito
A1 Shuhei Yoshida
A1 Haruki Matsumoto
A1 Jumpei Temmoku
A1 Yuya Fujita
A1 Tomoyuki Asano
A1 Kiyoshi Migita
YR 2023
UL http://lupus.bmj.com/content/10/1/e000870.abstract
AB 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.Data are available on reasonable request.