Transcription factor Fli-1 impacts IL-17 expression and affects immune cell infiltration into the kidney in lupus-prone mice

Abstract

Abstract Objectives Transcription factor Fli-1 affects lupus nephritis development through regulating several cytokines and chemokines. Th17 immune response is important to maintain inflammation in lupus nephritis. The purpose of this study is to elucidate whether Fli-1 affects renal IL-17 expression and influence immune cell infiltration into the kidney. Methods Sera were collected from Fli-1-heterozygous (Fli-1+/−) MRL/lpr mice and wild-type (WT) littermates, and the concentration of IL-17 was measured by enzyme-linked immunosorbent assay. Expression of IL-17 and related molecules were measured by real-time polymerase chain reaction (rt-PCR) analysis. Kidneys from Fli-1+/− and WT MRL/lpr mice were stained and evaluated the grade of inflammation. IL-17 expression was detected using anti-mouse IL-17 antibodies. Immunofluorescence staining was performed using anti-CD3, CD4, and anti-IL-17 antibodies to detect T cells related to Th17 responses. In addition, to detect CCL20 expression as a chemoattractant of Th17 cells, anti-CCL20 antibodies and anti-CD11b antibodies were used to detect monocytes expressed CCL20. Results Fli-1+/− MRL/lpr mice had tendency of decreased serum IL-17 levels. Expression of IL-17 was significantly decreased in Fli-1+/− MR/lpr mice kidney interstitium, accompanied by decreased IL-6, STAT3, and IL-1β expression by rt-PCR. CD3 or CD4/IL-17 double-positive immune cells were significantly decreased in Fli-1+/− MLR/lpr mice; similarly, CCL20 positive monocytes were significantly decreased. Conclusion Fli-1 impacts IL-17 expression into the kidney of MRL/lpr mice by reducing CD3 and CD4 positive lymphocytes expressing IL-17 as well as CD11b positive monocytes expressing CCL20.