The effect of PU.1 inhibitors on the immune function of MRL/lpr mice
10.19405/j.cnki.issn1000-1492.2025.08.019
- VernacularTitle:PU.1抑制剂对MRL/lpr小鼠免疫功能的作用
- Author:
Tingting GUO
1
;
Nuo XU
;
Kang WANG
;
Ying LI
;
Wei WEI
;
Shangxue YAN
Author Information
1. 安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,安徽省抗炎免疫药物协同创新中心,合肥 230032
- Publication Type:Journal Article
- Keywords:
systemic lupus erythematosus;
PU.1 inhibitor;
TACI-Ig;
PU.1;
MRL/lpr mice;
immune function
- From:
Acta Universitatis Medicinalis Anhui
2025;60(8):1498-1505
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the impacts and fundamental mechanisms of the PU.1 inhibitor DB2313 on the immune function in MRL/lpr mice.Methods A total of thirty MRL/lpr lupus mice were randomly distributed into three separate groups:the model control group,the PU.1 inhibitor DB2313 treatment group(administered at a dose of 17 mg/kg),and the positive drug control Telitacicept(TACI-Ig)group(administered at a dose of 7.5 mg/kg).Furthermore,a group of ten BALB/c mice were assigned as the normal group.The DB2313 administration group was treated with intraperitoneal injections of the drug on three occasions per week,while the TACI-Ig group received subcutaneous injections every second day;both treatment protocols were maintained for a duration of five weeks.Both the control group and the model group were administered intraperitoneal injections of a volume of sa-line that was equivalent across groups.After the drug was given,mice were sacrificed by dislocation after orbital vein blood collection.The thymus and spleen were aseptically excised,individually weighed,and subsequently uti-lized to compute the thymus index and spleen index.The relative distribution of T lymphocyte subsets within the spleen was ascertained through flow cytometry.Serum concentrations of anti-nuclear antibodies(ANA)and anti-double-stranded DNA antibodies were quantified using an enzyme-linked immunosorbent assay(ELISA).The lev-els of inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)were meas-ured by CBA method.Hematoxylin and eosin(HE)staining was employed to examine pathological alterations in the spleen.The expression of PU.1 and IL-9 in spleen tissue was detected using immunohistochemistry.Addition-ally,the expression level of PU.1 protein in the spleen tissue was ascertained through Western blot analysis.Re-sults The administration of DB2313 significantly ameliorated spleen lesions in MRL/lpr mice and decreased the levels of anti-ds-DNA,ANA,TNF-α,IL-6,and IFN-γ.It also reduced the proportion of total T cells,TFH cells,Th17 cells,and Th9 cells in the mouse spleen,while increasing the proportion of Treg cells.Furthermore,it low-ered the level of PU.1 protein in the spleen.Immunohistochemistry results demonstrated that DB2313 treatment sig-nificantly diminished the expression of PU.1 and IL-9 in spleen tissue.Conclusion The PU.1 inhibitor DB2313 can improve spleen lesions in MRL/lpr mice and slow the progression of the disease,and its mechanism is related to the regulation of immune cell functions.
