旋毛虫感染对胶原诱导性关节炎小鼠肠道菌群的影响

寄生蠕虫能否通过调节宿主肠道菌群进而改善炎症性疾病是近年的研究热点。为探讨旋毛虫感染对胶原诱导性关节炎(Collagen-Ⅱinduced arthritis,CIA)小鼠肠道菌群构成和丰度的影响,将15只小鼠随机分为正常对照组、关节炎(CIA)组和预先感染旋毛虫关节炎(CIA.TS)组,在首次胶原诱导后第50 d,取小鼠粪便进行16S rDNA测序,然后将CIA组和对照组之间的差异菌属与关节炎评分进行Spearman相关分析。结果显示,与对照组相比,CIA组小鼠菌群结构发生了明显的改变,其丰富度和多样性有上升趋势;在门水平上,脱铁杆菌门、变形菌门和梭杆菌门的丰度明显增加;在属水平上,未分类毛螺菌科、Mucispirillum属和脱硫弧菌属的丰度明显增加,Alistipes属和理研菌属的丰度明显减少。CIA组小鼠中丰度显著升高的菌属,其相对丰度与关节炎评分呈正相关;而丰度显著降低的菌属,其相对丰度与关节炎评分呈负相关。与CIA组相比,预先感染旋毛虫的关节炎小鼠(CIA.TS)菌群的丰富度和多样性有下降趋势,脱铁杆菌门和变形菌门的丰度明显减少,Mucispirillum属和脱硫弧菌属的丰度明显减少,理研菌属的丰度明显增加。以上结果表明,CIA小鼠肠道菌群结构改变与关节炎疾病严重程度密切相关,而预先感染旋毛虫可缓解CIA小鼠的关节炎症,其改善作用可能与调节CIA小鼠肠道菌群结构有关。     

组蛋白去乙酰化酶抑制剂TSA对小鼠胶原诱导性关节炎的治疗作用

目的 研究组蛋白去乙酰酶化抑制剂制滴菌素A(TSA)对小鼠胶原诱导性关节炎的作用,初步探讨其作用机制.方法 将雄性DBA/1小鼠随机分为胶原诱导性关节炎(CIA)模型组、预防性给药组、治疗性给药组、正常组.免疫后第35天处死小鼠,检测小鼠足爪炎症的肿胀度,病理切片观察炎症变化,MTT法检测脾淋巴细胞对胶原的增殖反应,实时荧光定量PCR检测TSA对小鼠脾细胞IFN-γ、IL-4 mRNA表达的影响,ELISA检测IFN-γ、IL-4的含量.结果 CIA模型组关节炎评分、对CⅡ的增殖反应、IFN-γ水平均高于正常对照组;给药组关节炎评分、对CⅡ的增殖反应低于CIA模型组;给药组IFN-γ水平低于CIA组,但IL-4水平高于CIA组.结论 TSA对CIA具有抑制作用,其可能机制是抑制T细胞的活化、增殖,调节Th1/Th2的失衡状态.     

嗜碱粒细胞在胶原诱导性关节炎小鼠发病早期中的作用

用鸡Ⅱ型胶原免疫C57BL/6小鼠,制备胶原诱导性关节炎(collagen induced arthritis,CIA)小鼠模型。用MAR-1抗体清除嗜碱粒细胞,以同型抗体为对照。记录各组小鼠关节炎指数(arthritis index,AI)的变化。ELISA法检测血清抗Ⅱ型胶原抗体、IL-4、IL-6和IFN-γ水平。小鼠关节标本用HE染色进行病理分析。探讨嗜碱粒细胞在胶原诱导性关节炎小鼠发病早期中的作用。结果显示,成功建立CIA小鼠模型。清除嗜碱粒细胞组、模型对照组和MAR-1抗体同型对照组相比,清除嗜碱粒细胞可显著抑制关节炎指数的升高,显著降低抗Ⅱ型胶原的抗体水平以及血清IL-4的水平,但对IL-6和IFN-γ的水平无影响。同时,清除嗜碱粒细胞可显著改善CIA模型小鼠的关节外观和关节病理改变。研究表明,靶向清除嗜碱粒细胞可减轻CIA模型小鼠的早期发病症状,可能与其介导IL-4生成和自身抗体产生相关。     

T细胞疫苗对CIA的免疫调节作用

目的探讨T细胞疫苗(TCV)对小鼠胶原诱导性关节炎(CIA)的免疫调节作用。方法通过TCV干预CIA模型,观察小鼠发病情况,运用免疫组化技术观察局部关节病变程度;FACs分析T细胞亚群变化;ELISA检测细胞培养上清中TGF-β、IFN-γ、IL-17水平;定量PCR方法检测Treg、Th1、Th17细胞相关转录因子表达水平。结果经过TCV干预,小鼠自身反应性T细胞的增殖能力被显著抑制,CII抗体水平也显著下降;相较CIA组,TCV组Treg细胞百分比上升,Th1、Th17细胞百分比明显降低;各细胞分泌细胞因子的能力也发生相应的变化,其中TGF-β上升,IFN-γ、IL-17降低;Treg细胞转录因子Foxp3基因水平提高,Th1、Th17细胞转录因子T-bet、RORα及RORγt的mRNA水平降低。结论 TCV干预可通过抑制CIA小鼠自身反应性T细胞增殖,上调小鼠体内Treg细胞并抑制Th1、Th17细胞的表达而发挥免疫调节作用,有效降低小鼠发病严重度和关节炎症。     

雷帕霉素联合人脐带血CD4~+ CD25~+调节性T细胞治疗胶原诱导性关节炎小鼠的初步研究

目的:初步探讨雷帕霉素(Rapa)联合人脐带血CD4+CD25+调节性T细胞(Tregs)对胶原诱导性关节炎小鼠的治疗作用。方法:通过体外扩增培养获得人脐带血Tregs;建立牛Ⅱ型胶原诱导的类风湿性关节炎(CIA)小鼠模型;将CIA小鼠随机分为对照组,Tregs治疗组,Rapa治疗组,Tregs与Rapa联合治疗组;小鼠骨关节切片进行Safranin O-fast green染色、甲苯胺蓝染色以及HE染色;ELISA法检测CIA小鼠血浆抗Ⅱ型胶原抗体浓度;流式细胞术检测CIA小鼠脾脏CD4+T细胞亚型;检测Tregs在体外对CIA小鼠Ⅱ型胶原特异性CD4+T细胞增殖的抑制功能;Transwell分隔培养法比较非接触培养与直接接触培养中Tregs对CD4+T细胞增殖抑制作用的差异。结果:Tregs与Rapa联合治疗能够延缓疾病发生,显著降低关节炎评分,减少CIA小鼠关节中软骨的破坏以及炎症细胞浸润,降低CIA小鼠血浆中抗胶原总IgG抗体水平以及脾脏中Th17细胞比例;Tregs在体外能够有效抑制CIA小鼠胶原特异性CD4+T细胞的增殖,这种抑制作用主要可能是通过直接接触抑制途径起作用。结论:雷帕霉素联合人脐带血Tregs治疗能够改善CIA小鼠关节炎症状。     

黄芩茎叶总黄酮对胶原性关节炎小鼠Th1/Th2细胞平衡的调节

目的观察黄芩茎叶总黄酮对Ⅱ型胶原诱导性关节炎小鼠脾淋巴细胞Th1、Th2及其相关细胞因子IL-10、IFN-γ的影响,初步探讨黄芩茎叶总黄酮对类风湿性关节炎的作用。方法选用C57BL/6小鼠,建立鸡Ⅱ型胶原诱导性关节炎小鼠模型,将造模成功的小鼠随机分为CIA模型组、黄芩茎叶总黄酮组、雷公藤多苷组,另设正常对照组,于初次免疫后第21天开始灌胃给药,35 d后流式细胞术检测小鼠脾淋巴细胞Th1、Th2水平及相关细胞因子IL-10、IFN-γ的表达。结果与模型组比较,药物组小鼠CD4+T淋巴细胞中Th1细胞数量明显降低(P0.05),Th2比例增加(P0.01),药物组IL-10分泌显著增多(P0.05),IFN-γ分泌明显减少(P0.05),2用药组无明显差异(P0.05)。结论黄芩茎叶总黄酮可以调节Th1/Th2的平衡及其相关细胞因子IFN-γ、IL-10的表达。     

非T细胞结合肽(FNS007)对关节炎小鼠病程及骨损伤的影响

目的观察非T细胞结合肽(FNS007,又称NTAP)对Ⅱ型胶原(collagen typeⅡ,CⅡ)诱导的关节炎(collagen-induced arthritis,CIA)小鼠炎症反应及骨损伤的影响,并探讨其作用机制。方法采用Ⅱ型胶原诱导建立CIA小鼠模型。发病小鼠随机分为模型组、FNS007 1.2、2.4、4.8 mg/kg(低、中、高)剂量组及阳性药阿巴西普(5 mg/kg)组,另设正常对照组,尾静脉注射给药,隔天1次,直至治疗结束。给药后第28天处死小鼠。给药期间每日评价各组小鼠四爪的关节炎临床评分;治疗结束后,通过X光、显微计算机断层扫描(micro-computed tomography,Micro-CT)及三维重建对小鼠四爪进行骨损伤评价以及骨参数分析。结果与模型组比较,FNS007明显降低CIA小鼠关节炎临床炎症评分;X光结果显示,FNS007明显减轻CIA小鼠四爪骨损伤程度;FNS007组小鼠micro-CT评分及骨表面积与骨体积比(BS/BV)明显降低,组织矿物质密度(TMD)及骨小梁厚度(Tb.Th)明显升高。结论 FNS007可明显抑制胶原性关节炎小鼠的关节炎症,改善关节组织损伤和骨破坏。     

高密度脂蛋白改善胶原诱导性关节炎模型小鼠的症状

目的探讨高密度脂蛋白(HDL)对胶原诱导性关节炎(CIA)小鼠的作用。方法将小鼠随机分为对照组、CIA组、CIA+HDL组。应用Ⅱ型胶原蛋白诱导建立关节炎小鼠模型,尾静脉注射高密度脂蛋白(10 mg/kg),每3 d注射1次,共注射5次。期间记录小鼠体质量变化和关节炎临床评分。第75天处死小鼠,使用ELISA试剂盒测定小鼠血清中肿瘤坏死因子-α(TNF-α)、Ⅱ型胶原特异性抗体IgG2α的水平,将小鼠踝关节组织切片用HE染色,分析各组小鼠类风湿性关节炎的严重程度以评价高密度脂蛋白对于类风湿性关节炎的作用。结果与CIA组相比,静脉注射10 mg/kg的HDL可以显著改善小鼠类风湿性关节炎的症状。实验结果显示HDL可以减轻关节炎临床症状,降低血清中促炎因子TNF-α以及特异性抗体IgG2α表达水平(P0.05)。病理组织学检测显示HDL可以使小鼠踝关节关节面变光滑,明显改善滑膜增生、炎性细胞浸润与骨侵蚀等病理变化。结论 HDL对类风湿性关节炎小鼠的症状有显著的改善作用。     

THH对胶原诱导型关节炎小鼠Th17细胞及细胞因子的影响

目的通过观察昆明山海棠(Tripterygium hypoglaucum hutch,THH)对胶原诱导型关节炎(collagen induced arthritis,CIA)小鼠Th17细胞及相关炎性细胞因子的影响,探讨THH治疗类风湿关节炎的相关免疫学机制。方法 30只健康雄性C57BL/6小鼠随机选取10只作为正常对照组,剩余20只用于制备CIA小鼠模型。将造模成功的小鼠随机分为CIA模型组、THH治疗组,每组9只。通过观测小鼠体质量、关节炎指数评分、关节肿胀程度及HE染色了解THH治疗情况,利用流式细胞术、实时荧光定量PCR(RT-qPCR)及ELISA观察THH对CIA小鼠Th17细胞及IL-17A的影响,并使用GraphPad软件对结果进行分析。结果CIA模型组小鼠体质量与THH治疗组间无统计学差异;关节炎指数评分及关节肿胀程度CIA模型组均高于THH治疗组;HE染色显示THH治疗组关节炎的炎症较模型组减轻,骨损伤减少。流式结果显示,脾脏Th17细胞比例CIA模型组低于正常对照组(P0.01),THH治疗组高于CIA模型组(P0.05)。CIA模型组踝关节及血清中IL-17A表达明显高于正常对照组(P0.01),THH治疗组中的表达量低于CIA模型组(P0.05)。结论 THH可通过升高CIA小鼠外周免疫器官Th17细胞比例、降低关节组织及血清IL-17A表达水平,从而减轻关节炎的炎症反应,减少关节骨损伤。     

卡介苗在关节炎模型小鼠诱导中的作用

目的：探讨在牛Ⅱ型胶原诱导性关节炎模型（ Collagen-induced arthritis ,CIA）小鼠的诱导过程中,弗氏完全佐剂（ FCA）中的卡介苗（ BCG）浓度和CIA小鼠关节炎严重程度的关系。方法：将牛Ⅱ型胶原蛋白溶液与含不同BCG的FCA等体积混合乳化,在小鼠尾根部注射进行免疫。免疫后观察小鼠的相关指标包括体重、发病率、血清TNF-α、关节炎指数及小鼠关节和脾脏的病理变化。结果：与1 mg/ml卡介苗组相比,4 mg/ml卡介苗组诱导的CIA小鼠发病早,关节炎指数、关节和脾脏病理评分升高及小鼠体重下降更明显,血清TGF-α明显升高,差异有统计学意义。结论：在进行CIA小鼠诱导时,BCG浓度和CIA小鼠关节炎严重程度呈正相关,实验中可以根据对动物的要求,选择含不同BCG的佐剂来诱导CIA小鼠。     

APRIL (TNFSF13) regulates collagen‐induced arthritis,IL‐17 production and Th2 response

A proliferation‐inducing ligand (APRIL or TNFSF13) shares receptors with B‐cell activation factor of the TNF family (BAFF) on B and T cells. Although much is known about the function of APRIL in B cells, its role in T cells remains unclear. Blocking both BAFF and APRIL suggested that BAFF and/or APRIL contributed to collagen‐induced arthritis (CIA); however, the role of APRIL alone in CIA remained unresolved. We show here that, in vitro, our newly generated APRIL^?/? mice exhibited increased T‐cell proliferation, enhanced Th2 cytokine production under non‐polarizing conditions, and augmented IL‐13 and IL‐17 production under Th2 polarizing conditions. Upon immunization with OVA and aluminum potassium sulfate, APRIL^?/? mice responded with an increased antigen‐specific IgG1 response. We also show that in APRIL^?/? mice, the incidence of CIA was significantly reduced compared with WT mice in parallel with diminished levels of antigen‐specific IgG2a autoantibody and IL‐17 production. Our data indicate that APRIL plays an important role in the regulation of cytokine production and that APRIL‐triggered signals contribute to arthritis. Blockade of APRIL thus may be a valuable adjunct in the treatment of rheumatoid arthritis.     

Conversion in vivo from an early dominant Th0/Th1 response to a Th2 phenotype during the development of collagen-induced arthritis

Over the past decade, the central role of T cells in the process of collagen-induced arthritis (CIA) has been extensively documented. The inflammatory features of CIA and its successful modulation after treatment in vivo with Th2 lymphokines, known to down-regulate proinflammatory cytokines, classify CIA as a Th1-mediated disease. However, no direct evidence for the presence of the different T helper subsets has been obtained. To identify the collagen-specific CD4⁺ T cell subset(s) developing during the course of CIA, lymph nodes from susceptible DBA/1 mice (H-2q) were harvested at different times after injection of bovine type II collagen in Freund's complete adjuvant and checked by enzyme-linked immunospot assay for the production of interferon (IFN)-γ and interleukin (IL)-4. The results clearly showed that type II collagen-specific T cells secreting either IFN-γ, IL-4, or both, develop early in vivo, before the onset of arthritis: the number of IFN-γ-secreting cells was already maximal 15 days after immunization, whereas more IL-4-secreting cells were found at day 30, just before the onset of clinical arthritis. Another strategy was to establish collagen-specific CD4⁺ T cell lines and sublines in vitro and to analyze their lymphokine secretion pattern. Lines generated 8 days after immunization displayed a mixed lymphokine secretion pattern characteristic of Th0 cells or of a mixture of Th1 and Th2 cells. After limiting dilution of a day 8 line, 60% of the growing sublines were Th0-like (secreting IFN-γ, IL-4, and IL-5), and 25% were Th1 (secreting IFN-γ). By day 25 post-immunization, 33% of the generated sublines were Th0-like, 11% Th1, and 56% Th2 (secreting IL-4 and IL-5). Moreover, all the sublines raised from the lymph nodes of arthritic mice harvested at day 55 secreted high amounts of Th2 lymphokines, and only 3 out of 14 also produced some IFN-γ. This study demonstrates that during the course of CIA the collagen-specific CD4⁺ T cell response shifts in vivo from a dominant Th0/Th1 response to a clear Th2 phenotype. These results contribute to our understanding of the collagen-specific CD4⁺ T helper subsets which develop during the induction and clinical phases of CIA.     

Altered collagen II 263–272 peptide immunization induces inhibition of collagen-induced arthritis through a shift toward Th2-type response

To investigate the effects of altered collagen II (CII) peptide ligands in collagen-induced arthritis (CIA), CIA rats were subcutaneously injected with an altered CII263–272 peptide ligand (APL, 100, 10, and 1 μg/dose, six dose each, twice a week), which had been identified by us as an inhibitory effect on CII-specific T-cell activation in vitro in rheumatoid arthritis (RA). Clinical, radiographic, and histologic scores were evaluated. Serum level of interferon (IFN)-γ was assessed by enzyme-linked immunosorbent assay, and the numbers of interleukin (IL)-4-producing cells in vitro in memory responses to the APL were determined by enzyme-linked immunospot. The results showed significantly reduced arthritis scores in CIA rats treated with 100 μg/dose of APL compared with those treated with phosphate buffered solution (PBS) and control peptide. The mean radiographic and histologic scores were also markedly lower in APL-treated CIA rats. On day 35 after immunization, a significantly lower level of IFN-γ in serum was found in APL-treated rats, accompanied by increased numbers of IL-4-producing cells, indicating that APL treatment skewed the T helper (Th)1/Th2 balance toward Th2-type response in vivo . Altered CII263–272 peptide ligand immunization induces inhibition of CIA through a shift toward Th2-type response, suggesting that altered CII peptide might be a potential therapeutic target for RA.     

Dendritic cells modulated by innate immunity improve collagen-induced arthritis and induce regulatory T cells in vivo

Dendritic cells (DCs) mediate interactions between innate and specific immunity and may induce regulatory mechanisms. We investigated the effects of modulated DCs in mice with collagen-induced arthritis (CIA) and tested the responses of cells to induced naturally occurring regulatory T cells. DCs were stimulated or not with DNA or lipopolysaccharide (LPS) for 24 hr. DC maturation was assayed, and then modulated DCs were intraperitoneally injected on day 14 into DBA/1 mice to treat CIA. In addition to arthritis scores and type 2 collagen (CII) response, the induction of CD4(+) CD25(+) T cells was analysed by flow cytometry in peripheral blood and the expression of Foxp3, transforming growth factor (TGF)-beta, interleukin (IL)-10 and cytotoxic T-lymphocyte antigen (CTLA)-4 was quantified. Finally, the expression of indoleamine-2,3-dioxygenase (IDO) was assayed in DCs. In comparison with LPS-stimulated DCs, plasmid-stimulated DCs expressed lower levels of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86 molecules and secreted less IL-12p70, interferon (IFN)-gamma, IL-10 and TNF-alpha, displaying a semi-mature phenotype. Compared with non-stimulated DCs, stimulated DCs improved arthritis scores when injected after immunization, without modifying the T helper type 1 (Th1)/Th2 balance of the immune response against collagen. Stimulated DCs induced markers for regulatory T cells (Foxp3, TGF-beta1 and CTLA-4) in vivo. Only LPS-stimulated DCs expressed IDO, which may explain their better therapeutic efficacy. Regulatory mechanisms were induced using DCs modulated by innate immunity stimulators. Innate immunity mechanisms do not require the presence of the disease-causing antigen, even in T- and B-cell specific diseases. Our results have implications for the treatment of rheumatoid arthritis, an autoimmune disease whose triggering antigen has not been identified, and substantially clarify the role of regulatory T cells in CIA.     

旋毛虫对不同肠炎模型小鼠脾脏淋巴细胞Th1/Th2水平的影响

目的：研究旋毛虫（T.spiralis）对肠炎小鼠［三硝基苯磺酸（TNBS）或唑酮（OXZ）诱导］脾脏淋巴细胞中Th1/Th2水平的影响。方法：雌性BALB/c小鼠,随机分为50%乙醇对照组、TNBS(OXZ)诱导肠炎模型组、预先感染T.spiralis后诱导TNBS(OXZ)模型组,每组小鼠取材时保证6只以上。对各组小鼠脾脏淋巴细胞进行分离,采用流式细胞术观察TNBS（OXZ）诱导肠炎模型组和预先感染T.spiralis后诱导TNBS（OXZ）模型组。造模后3 d和7 d脾脏淋巴细胞中Th1/Th2水平的变化。结果：与模型组相比,预先感染T.spiralis后诱导TNBS肠炎第3天脾脏Th1/Th2比值未见明显下降（P>0.05）,于第7天明显降低（P<0.05）。诱导OXZ肠炎模型后第3天及第7天小鼠脾脏Th1/Th2比值均明显低于T.spiralis干预组（P<0.05）。结论：针对TNBS 肠炎模型,T.spiralis可能是通过诱导Th2及Tr1型免疫反应抑制模型小鼠过度的Th1型免疫而起到良好的干预作用。在T.spiralis对OXZ模型小鼠的干预性研究中,并无T.spiralis感染诱发的Th2型炎症反应加重同样以Th2升高为主的OXZ模型小鼠的病情。     

Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice

Collagen-induced arthritis (CIA) is an animal model for rheumatoid arthritis. The disease is elicited by immunization of genetically susceptible DBA/1 mice with type II collagen, resulting in a debilitating arthritis characterized by inflammation and involvement of multiple joints. We investigated the role of endogenous interleukin (IL)-12 in the pathogenesis of this disease by undertaking an analysis of IL-12-deficient mice on the DBA/1 genetic background after immunization with type II collagen. Both the incidence and severity of disease were significantly reduced in mice unable to produce biologically active IL-12. Concomitant decreases were observed in serum levels of pathogenic, collagen-specific IgG2a antibodies and collagen-induced secretion of interferon-γ by immune splenocytes in vitro, consistent with an impaired T helper-1 response. There were, however, a few animals which developed severe disease in a single paw in spite of this highly diminished Th1 response. Taken together, these results demonstrate an important role for IL-12 in the pathogenesis of CIA, although it is not absolutely required for disease development.     

Protection against collagen‐induced arthritis in mice afforded by the parasitic worm product,ES‐62, is associated with restoration of the levels of interleukin‐10‐producing B cells and reduced plasma cell infiltration of the joints

We have previously reported that ES‐62, a molecule secreted by the parasitic filarial nematode Acanthocheilonema viteae, protects mice from developing collagen‐induced arthritis (CIA). Together with increasing evidence that worm infection may protect against autoimmune conditions, this raises the possibility that ES‐62 may have therapeutic potential in rheumatoid arthritis and hence, it is important to fully understand its mechanism of action. To this end, we have established to date that ES‐62 protection in CIA is associated with suppressed T helper type 1 (Th1)/Th17 responses, reduced collagen‐specific IgG2a antibodies and increased interleukin‐10 (IL‐10) production by splenocytes. IL‐10‐producing regulatory B cells have been proposed to suppress pathogenic Th1/Th17 responses in CIA: interestingly therefore, although the levels of IL‐10‐producing B cells were decreased in the spleens of mice with CIA, ES‐62 was found to restore these to the levels found in naive mice. In addition, exposure to ES‐62 decreased effector B‐cell, particularly plasma cell, infiltration of the joints, and such infiltrating B cells showed dramatically reduced levels of Toll‐like receptor 4 and the activation markers, CD80 and CD86. Collectively, this induction of hyporesponsiveness of effector B‐cell responses, in the context of the resetting of the levels of IL‐10‐producing B cells, is suggestive of a modulation of the balance between effector and regulatory B‐cell responses that may contribute to ES‐62‐mediated suppression of CIA‐associated inflammation and inhibition of production of pathogenic collagen‐specific IgG2a antibodies.     

CARD11 blockade suppresses murine collagen‐induced arthritis via inhibiting CARD11/Bcl10 assembly and T helper type 17 response

The scaffold protein caspase recruitment domain‐containing protein 11 (CARD11) is implicated in the regulation of inflammation and autoimmunity. The present study aimed to explore the role of CARD11 in the pathogenesis of rheumatoid arthritis (RA). Mice with collagen‐induced arthritis (CIA) were treated with either CARD11‐targeted interfering RNA (CARD11 siRNA) or control siRNA by intraperitoneal injection every 3 days after CIA establishment. The clinical score of arthritis was recorded every other day. Synovial inflammation and cartilage erosion were evaluated by histology and microcomputed tomography (micro‐CT). Serum anti‐type II collagen (anti‐CII) antibodies and cytokines were measured by enzyme‐linked immunosorbent assay (ELISA). The CARD11/Bcl10 formation and nuclear factor‐kappa B (NF‐κB) activation was assessed by immunoprecipitation and immunoblotting, and the percentage of T helper type 17 (Th17) cells was determined by flow cytometry. Systemic administration of CARD11 siRNA significantly reduced the clinical score of CIA severity. As indicated by the histology, joint inflammation and destruction were attenuated by CARD11 siRNA treatment. Micro‐CT demonstrated less severe joint destruction in CARD11 siRNA‐treated mice than in control mice. CARD11 siRNA treatment resulted in inhibition of CARD11/Bcl10 formation and the subsequent NF‐κB activation. In addition, treatment with CARD11 siRNA resulted in a pronounced decrease in proinflammatory cytokines interleukin (IL)‐1β, IL‐6 and IL‐17. Serum anti‐CII antibody and the percentage of Th17 cells were also significantly reduced. CARD11 is involved in the pathogenesis of CIA by formation of the CARD11/Bcl10 complex and enhancement of the Th17 cell response. Targeting CARD11 provides a novel research direction in the development of therapeutic strategies for RA.