皮肤性病诊疗学杂志2025，Vol.32Issue(12)：837-845,9.DOI:10.3969/j.issn.1674-8468.2025.12.001
重组锚蛋白重复结构域蛋白22通过靶向抑制非经典NF-κB信号通路缓解小鼠的银屑病进程
ANKRD22 recombinant protein attenuates psoriasis in mice through inhibiting noncanonical NF-κB signaling pathway
摘要
Abstract
Objective To elucidate the anti-inflammatory effects and underlying molecular mechanisms of recombinant ANKRD22 protein in dendritic cells,and to assess its therapeutic effi-cacy in mitigating the progression of psoriasis.Methods In vitro,mouse bone marrow cells isola-ted from femurs and tibias were induced into mature bone marrow-derived dendritic cells(BMDC)using GM-CSF.The BMDC were divided into four groups:PBS,IMQ,PBS+recombinant ANKRD22,and IMQ+recombinant ANKRD22.Each group was treated accordingly with PBS,IMQ,or recombinant ANKRD22 protein for 24 h.Quantitative reverse transcription PCR(qRT-PCR)was used to measure the expression levels of mRNA for IL23a,IL1 b,and ANKRD22,while Western blot was performed to detect the protein levels of key members of the noncanonical NF-κB signaling pathway.In vivo,an IMQ-induced mouse model of psoriasis was established(n=10)and divided into a PBS control group(n=5)and a recombinant ANKRD22 group(n=5).The changes in body weight and PASI scores were recorded daily.Histological changes and acanthosis area were evaluated by hematoxylin and eosin(H&E)staining.Flow cytometry was used to determine the proportions of neutrophils,Th17,and γδT17 cells,and qRT-PCR was used to quantify the expression levels of mRNA for IL1 b,IL23a,IL17a,IL17f,IL6 and TNF-α in the skin.Results In vitro,compared with the PBS group,expression levels of IL23a,IL1 b and ANKRD22 mRNA in the IMQ group significantly increased to 1.97±0.33(P=0.007),1.80±0.32(P=0.014)and 2.34±0.52(P=0.014)fold,accompanied by enhanced NIK accumulation and downstream p52/RelB nuclear translocation.In contrast,compared with the IMQ group,IL23a expression in the IMQ+recombinant ANKRD22 group was significantly reduced,from 1.97±0.33 to 1.17±0.19-fold(P=0.023),without significant differences in the expression levels of IL1 b and ANKRD22 mRNA.Concurrently,NIK accumulation and downstream p52/RelB nuclear translocation were markedly attenuated.In vivo,recombinant ANKRD22 significantly alle-viated psoriasis-like symptoms.On day 5,the PASI score was significantly lower in the recombi-nant ANKRD22 group than in the PBS group(6.10±0.65 vs.7.80±0.83,P=0.007),acan-thosis area was reduced from 0.08±0.01 to 0.04±0.01 mm2(P=0.001),and splenomegaly was mitigated with an increased body weight(20.24±0.51 g vs.19.06±0.45 g,P=0.005).The proportions of neutrophils,Th17,and γδT17 cells in the skin decreased from(21.00±3.07)%,(38.16±3.66)%,and(9.74±3.02)%to(6.48±1.96)%(P=0.001),(24.48±3.37)%(P=0.001),(6.42±1.55)%(P=0.030),respectively.The expression levels of mRNA for IL1 b,IL23a,IL17a,IL17f,IL6 and TNF-α in the skin were also reduced from(32.67±17.34)%to(67.37±25.43)%.Conclusions Recombinant ANKRD22 protein sup-presses IL-23 production by selectively inhibiting the noncanonical NF-κB signaling pathway in dendritic cells,thereby blocking the IL-23-Th17/γδT17 immune axis,promoting inflammatory resolution,and effectively ameliorating psoriasis progression.关键词
银屑病/锚蛋白重复结构域蛋白22/树突状细胞/炎症消退Key words
psoriasis/ANKRD22/dendritic cells/inflammation resolution引用本文复制引用
LIANG Kaiyu,JI Suyun,XIA Xichun..重组锚蛋白重复结构域蛋白22通过靶向抑制非经典NF-κB信号通路缓解小鼠的银屑病进程[J].皮肤性病诊疗学杂志,2025,32(12):837-845,9.基金项目
国家自然科学基金(82473514) （82473514）
广州市科技计划项目(2025A04J3957) （2025A04J3957）
