Search

In order to improve the dynamic performance and stability of general acceleration slip regulation (ASR) control technology for four-wheel independent drive electric vehicle (4WID EV), an ASR control strategy based on variable gain controller (VGC) is proposed in this paper. First of all, a road identification strategy is designed to identify the current road surface and calculate the optimal slip ratio of the road. Then, the optimal slip ratio is taken as the control target, and the ASR control strategy based on VGC is designed to keeps slip ratio around the optimum slip ratio through controlling the driving torque output, so wheels can make the best of road adhesion to prevent vehicle from slipping. Meanwhile, we analyze the control system state space, and build a scalar function of the system, and prove that the system satisfies Lyapunov large scale asymptotic stability theorem, so the parameters of the VGC does not affect the system stability. Then, in order to meet the requirement of quick dynamic response and no overshoot, parameters selection of VGC is deduced by mathematics. Finally, the co-simulation of Matlab/Simulink and Carsim results show that the proposed control strategy is with the better dynamics and stability, and can better prevent wheel slipping on various roads.

Wheel slipping of four-wheel independent drive electric vehicle on slope will reduce vehicle controllability and driving stability, thereby reducing vehicle safety. In order to solve the problem of wheel slipping and optimize the speed control performance of four-wheel independent drive electric vehicle on slope, an acceleration slip regulation control strategy of slope drive is proposed in this paper. First, we design a road identification algorithm to identify the current road conditions of the four-wheel independent drive electric vehicle, and calculate the optimal slip ratio of the current road surface by curve fitting method. Then, with the optimal slip ratio as the control objective, the acceleration slip regulation control strategy is designed to maximize the utilization of wheel adhesion coefficient to prevent wheel slip. Third, a slope identification algorithm based on Luenberger state observer is designed to identify the various slopes of the uphill and downhill road, after which a torque compensation algorithm is designed according to the identification slope, to compensate for the longitudinal component of vehicle gravity at different slopes. Fourth, a slope torque distribution algorithm is proposed based on acceleration slip regulation and slope identification. Finally, through the joint simulation platform of MATLAB/Simulink and CarSim, it is shown that the proposed control strategy can better restrain wheel slipping on the uphill and downhill road, and has better dynamic characteristics and stability.

A novel speed control scheme combining adaptive speed controller and radial basis function neural network (ASC-RBFNN) is proposed for the speed regulation of permanent magnet synchronous motor (PMSM) in this paper. On one hand, in order to reduce the effect of parametric uncertainty and complicated load fluctuation on the speed control performance, an ASC is proposed. Meanwhile, the speed control system (SCS) of PMSM with the proposed ASC is asymptotically stable even though the parametric uncertainty and complicated load fluctuation exist. On the other hand, with consideration of the uncertainty of complicated load, PMSM parameters, and ASC parameters, the RBFNN is used to optimize all ASC parameters for optimal speed control performance. Finally, the performance is verified on an experiment platform. The results indicate that the SCS with the ASC-RBFNN speed control scheme is with good system stability, fast speed response, and strong anti-fluctuation performance in whole-speed range.

Background Neutrophilic inflammation in the airway is a hallmark of bronchiectasis. Neutrophil extracellular traps (NETs) have been reported to play an important role in the occurrence and development of bronchiectasis. Neutrophil side fluorescence is one of the characteristics of neutrophils that can reflect the activation of neutrophils and the formation of NETs. Objective To explore the relationship between the values of neutrophil side fluorescence (NEUT-SFL) in the peripheral blood of bronchiectasis patients, and the severity of the disease. Methods 82 patients with bronchiectasis from the Department of Respiratory and Critical Medicine, at the Third Affiliated Hospital of Southern Medical University and were scored with Bronchiectasis Severity Index (BSI) (2019–2021). The clinical data such as the value of NEUT-SFL, neutrophil count, C-reactive protein, and procalcitonin levels were collected and retrospectively analyzed. NEUT-SFL values neutrophil count from 28 healthy subjects were also used to ascertain cut-off values. Results Based on the BSI scores, patients were divided into three categories as mild (32%), moderate (29%), and severe (39%). Our results showed that the values of NEUT-SFL were higher in bronchiectasis patients compared to healthy controls. The levels of NEUT-SFL positively correlated with the high BSI scores in patients (P = 0.037, r = 0.23) and negatively correlated with the lung function in these patients (r = − 0.35, P = 0.001). The area under the ROC curve was 0.813, the best cut-off was 42.145, indicating that NEUT-SFL values > 42.145 can potentially predict the severity of bronchiectasis. Conclusions The values of NEUT-SFL in the peripheral blood can be used for predicting the severity of bronchiectasis.

To determine the role of gasdermin E (GSDME)-mediated pyroptosis in the pathogenesis and progression of rheumatoid arthritis (RA), and to explore the potential of GSDME as a therapeutic target in RA.The expression and activation of caspase 3 and GSDME in the synovium, macrophages, and monocytes of RA patients were determined by immunohistochemistry, immunofluorescence, and Western blot analysis. The correlation of activated GSDME with RA disease activity was evaluated. The pyroptotic ability of monocytes from RA patients was tested, and the effect of tumor necrosis factor (TNF) on caspase 3/GSDME-mediated pyroptosis of monocytes and macrophages was investigated. In addition, collagen-induced arthritis (CIA) was induced in mice lacking Gsdme, and the incidence and severity of arthritis were assessed.Compared to cells from healthy controls, monocytes and synovial macrophages from RA patients showed increased expression of activated caspase 3, GSDME, and the N-terminal fragment of GSDME (GSDME-N). The expression of GSDME-N in monocytes from RA patients correlated positively with disease activity. Monocytes from RA patients with higher GSDME levels were more susceptible to pyroptosis. Furthermore, TNF induced pyroptosis in monocytes and macrophages by activating the caspase 3/GSDME pathway. The use of a caspase 3 inhibitor and silencing of GSDME significantly blocked TNF-induced pyroptosis. Gsdme deficiency effectively alleviated arthritis in a mouse model of CIA.These results support the notion of a pathogenic role of GSDME in RA and provide an alternative mechanism for RA pathogenesis involving TNF, which activates GSDME-mediated pyroptosis of monocytes and macrophages in RA. In addition, targeting GSDME might be a potential therapeutic approach for RA.

Graphical abstract DCs act as sentinels for the immune system. DCs capture antigens locally and become mature, characterized by up-regulation of chemokine receptors (CCR7 and CXCR4), adhesion molecule (L-selectin), co-stimulator molecules (CD40, CD80 and CD86) and MHC II. Under high concentration of CCL21 in draining lymph nodes (LNs), mature DCs traffic to LNs via afferent lymph vessels and present antigens to T cells, resulting in the development of arthritis. HCQ impaires DC maturation via blocking TLR9 signaling, retrains DC migration to LNs, and prevents the initiation and progression of RA., Highlights • HCQ efficiently inhibited DC phenotypic and functional maturation stimulated by serum from RA patients. • HCQ prevented progression of arthritis by inhibiting DC maturation and migration from peripheral blood to LNs. • HCQ inhibited CpG ODN 1826-activated BMDC maturation and migration. • The effect of HCQ on DCs was related to the block in TLR9 signaling. • The development of arthritis was impaired in TLR9−/− mice., Hydroxychloroquine (HCQ) is one of the most commonly prescribed immune-suppressants in treating rheumatoid arthritis (RA). Our previous research showed that HCQ suppressed RA development by inhibiting T follicular helper (Tfh) cells directly. Dendritic cells (DCs) serve as the link between innate and acquired immunity. Whether HCQ suppressed Tfh cell through DCs was not clear. In current study, we found that HCQ efficiently inhibited CD86, chemokine (C-X-C motif) receptor 4 (CXCR4) expression and interferon-α (IFN-α) secretion of healthy donor derived purified DCs stimulated by RA patient serum. To mimic RA, collagen-induced arthritis (CIA) mouse model was used and treated with HCQ daily for fifty-four days prior to sacrifice. We found HCQ inhibited DC maturation and migration to lymph nodes (LNs), manifested as down-regulated expression of CD40, CD80, CD86, MHCII (I-Aq) on LN DCs. In addition, HCQ reduced the level of chemokine receptor 7 (CCR7) and L-selectin on peripheral blood DCs and diminished percentage of LN DCs. Of note, HCQ only inhibited CpG ODN 1826-induced IL-12 secretion by bone marrow DCs (BMDCs) stimulated by various toll like receptor (TLR) agonists. Mechanistically, HCQ down-regulated the expression of TLR9 not only in healthy donor PBMC-derived DCs stimulated by RA patient serum, but also in LN DCs of CIA mice and CpG-activated BMDCs. Furthermore, arthritis scores in TLR9−/− mice were much lower than that in wild type mice with impaired maturity and migration capability of DCs. Collectively, activation of DCs contributes to the pathogenesis of RA and HCQ shows protective effects on RA by inhibition of DC activation via blocking TLR9.

Background Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis; however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE. Methods Real-time transcription-polymerase chain reaction (RT-PCR) analysis was used to determine the expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA), and 30 age- and sex-matched healthy controls (HC). Spearman’s correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value. Results Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for antinuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r = 0.3577, p = 0.0237), erythrocyte sedimentation rate (ESR) (r = 0.4091, p = 0.0043), serum immunoglobulin G (IgG) concentration (r = 0.3546, p = 0.0289), and the numbers of positive antinuclear antibodies (ANAs) (r = 0.3945, p = 0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779–0.9775, p Conclusions These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.

Activation of the coagulation system has been related to disease activity in some inflammatory diseases. Here, we aimed to investigate the relationship between coagulation function and the disease activity of axial spondyloarthritis (axSpA).This study retrospectively recruited 144 axSpA patients and 55 healthy controls. The patients were divided into an active group (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI ≥ 4) and a remission group (BASDAI 4). The coagulation, inflammatory and clinical parameters were detected. The correlations between these parameters were analyzed with Spearman's correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to compare the values of these variables in discriminating disease activity. Furthermore, binary logistic regression analysis was used to assess the risk factors for axSpA disease activity.Fibrinogen (FIB) was increased in the axSpA group compared to healthy controls (P 0.001). Additionally, FIB and D-dimer were higher in the active group than in the remission group (P 0.05, respectively). FIB and D-dimer were positively correlated with ESR, CRP, BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) (P 0.05, respectively). The area under the curve (AUC) of FIB was higher than that of ESR, CRP and D-dimer. The optimal cut-off value of FIB was 3.23 g/L, with a specificity of 62.0% and sensitivity of 75.0%. FIB (OR = 4.335, 95% CI: 1.262-14.888, P = 0.020) and BASFI score (OR = 1.878, 95% CI: 1.441-2.448, P 0.001) were independent risk factors affecting disease activity.Activated coagulation is closely related to the disease activity of axSpA. FIB and D-dimer might be novel indicators for monitoring the disease activity of axSpA.

Wheels of four-wheel independent drive electric vehicle (4WID EV) can be controlled independently, therefore, the torque distribution strategy becomes more complex. In this paper, a torque distribution strategy based on the optimal energy consumption is proposed. Under the given total torque command, the torque needed to be distributed by the current four wheels will be calculated by the extremum optimization algorithm, so that the four wheels can work in the high efficiency as much as possible, and the 4WID EV energy consumption becomes lowest. The simulation results showed that the torque distribution strategy proposed in this paper could significantly reduce energy consumption. Compared with torque average distribution strategy, the conventional method, this distribution strategy can save maximum energy 26.04% when the vehicle speed is between 20-100km/h.

This paper focuses on a class of control system of permanent magnet synchronous motor (PMSM) with the time delay link. Because of the delay of the inverter, the delay of the conditioning circuit, and the dead zone, there is a time delay between the input voltages of the motor and the output voltages of the controller. However, this time delay link is ignored in conventional vector control algorithms with respect to the d-q model, which inevitably leads to poor system stability and even divergence. In order to solve this problem, a novel control algorithm based on the mathematical model considering the time delay link is proposed in this paper. On one hand, the nonlinear time delay link is linearized and converted into a first-order inertial link through the Taylor series expansion method. Thus, nonlinear d-loop and q-loop are linearized. But the systems are changed into second-order systems. On the other hand, proportional-integral (PI) controllers with respect to the third-order optimum design method are designed to solve the design problem of controllers for higher-order systems than the conventionally d-q model. Experimental results show that the control algorithm proposed in this paper has good system stability with small current fluctuations, torque fluctuations, and speed fluctuations.

This paper focuses on the anti-fluctuation control of electric vehicle (EV) with the viscous friction coefficient and load fluctuations. Complicated load fluctuations inevitably leads to poor system performance with large speed fluctuations, slow speed response, poor operation stability and bad driving experience. In order to solve this problem, with consideration of the viscous friction coefficient, the mathematical model of PMSM for EV is established. Furthermore, a novel load observer based on the inverse model of the established model is designed to estimate load fluctuations, and the estimation is used as a feedback compensation for electromagnetic torque to reject load fluctuations. The simulation results demonstrate that load fluctuations can be estimated through the load observer accurately and quickly, and the proposed method has strong anti-fluctuation performance with fast speed response and small speed fluctuations. Thus, the operation stability and driving experience are improved for load fluctuations.

Hydroxychloroquine (HCQ) is an immunosuppressive agent widely used in rheumatoid arthritis (RA). T follicular helper (Tfh) cells play a vital role in the pathogenesis of RA. However, whether HCQ suppresses arthritis development through interfering with Tfh cells have never been reported. To address this issue, we investigated the percent of Tfh cells in newly diagnosed RA patients and found that they were up-regulated in peripheral blood. Importantly, in ex vivo experiments of peripheral blood mononuclear cells (PBMCs) from healthy volunteers, we proved that the percentage of Tfh cells in PBMCs and purified CD4+ T cells were decreased after HCQ treatment. In in vivo experiments of collagen-induced arthritis (CIA) model, we discovered that HCQ suppressed the incidence and score of arthritis, reduced the secretion of proinflammatory cytokines in serum. Similar to ex vivo study, the ratio of Tfh cells in HCQ treated CIA mice declined to the level of vehicle-treated group. Further research demonstrated that HCQ inhibited the generation of Tfh cells stimulated by IL-12 and IL-21. In conclusion, our study indicates a previously unrecognized mechanism of HCQ in RA, that HCQ directly suppresses the generation of Tfh cells by blocking IL-12 and IL-21 signaling pathways probably.

Career situation of first and presenting author Student for a master or a PhD. Introduction Neutrophilic asthma is Corticosteroid-resistant and increases the burden of global health care. Multiple studies have indicated that there are a large amount of neutrophil extracellular traps (NETs) in the airways of neutrophil asthmatics.1 Although NETs are able to entrap and kill pathogens, extensive accumulation of NETs which aggravate the condition of asthmatics and promote the progression of the disease.2 However to our knowledge, the mechanisms by which NETs influence the progression of asthma have not been clearly elucidated and neutrophilic asthma requires novel effective therapeutic strategies. Objectives We sought to explore the underlying mechanisms of NETs aggravate the severity of asthma, and to investigate a new strategy of effective treatment against corticosteroid-insensitive neutrophilic asthma. Methods Mouse models of neutrophil-dominated asthma and phorbolester(PMA) aggravated neutrophil asthma were used in this study to clarify the role of NETs in the pathogenesis of neutrophil asthma. Neutrophil release NETs was detected in bronchoalveolar lavage fluid (BALF)of neutrophil-dominated asthma. Finally a small molecule Necrostatin-1(Nec-1) which has been shown to inhibit neutrophil release NETs was tested for its therapeutic effects against neutrophilic airway inflammation. Results NETs could induce human epithelium human bronchial epithelial cell deth and detachment in vitro study. NETs significantly increased in neutrophil asthma model and PMA aggravated neutrophil asthma. In vivo studies, Nec-1 could relieve airway hyperresponse, also reduced total protein, myeloperoxidase activity and inflammatory cytokines. Histological examination of the lungs also showed that Nec-1 markedly reduced the inflammation. We further explored that Nec-1 could induce human neutrohils and mice BALF neutrohils apoptosis. BALF and lung tissue immunofluorescence showed neutrophils increased expression of cleaved-casepase.3 Conclusions NETs could damage airway epithelium and trigger inflammatory responses. Nec-1 inhibit neutrophil release NETs ameliorates neutrophil airway inflammation. May be the inherent mechanism of Nec-1 inhibit neutrophil release NETs is related to it specificitly promotes neutrophil apoptosis. References Porto BN, et al. Neutrophil Extracellular Traps in Pulmonary Diseases: Too Much of a Good Thing? Frontiers Immunolugy 2016;7:311. Toussaint M, et al. Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation. Nature Medicine, 2017;23(6):681–691. Pham, DL, et al. Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma. Clin Exp Allergy, 2017;47(1):57–70. Acknowledgements Thanks to the colleagues in the team of Dr Erwei Sun. Disclosure of Interest None declared.

Career situation of first and presenting author Young investigator. Introduction Evidences revealed that chemotherapies could trigger DNA release, then induce inflammation of intestinal tissues which damp the effect of anti-cancer treatment.1 2 DNA released induces the translocation of TLR9 to endolysosomes and subsequent nuclear factor-κB (NF-κB) activation, which leads to interleukin-1β (IL-1β) secretion and inflammation.3 Targeting TLR9-dependent DNA sensing pathway may be a valuable therapy for chemotherapy induced intestinal mucositis. Objectives This study aims to investigate whether hydroxychloroquine (HCQ), suppresses 5-FU-induced intestinal mucositis through inhibiting TLR9-dependent DNA sensing pathway. Methods The effect of HCQ on 5-FU-induced intestinal mucositis were examined in vivo and in vitro. We established 5-FU-induced intestinal mucositis model and assessed body weight, diarrhea score and histopathologic changes following HCQ treatment in vivo, then TLR9 and NF-κB expression of small intestine and IL-1β secretion of serum were analyzed. Bone marrow-derived macrophages (BMDMs) were cultured, transfected with calf-thymus DNA(CT-DNA) and treated with HCQ for 6 hour in vitro. TLR9 and NF-κB expression and IL-1β secretion in BMDMs were then investigated. Results HCQ treatment markedly attenuated body weight loss, severity of diarrhea, intestine shortening, and destruction of small intestinal in histopathology of 5-FU- treated mice in vivo. Also HCQ treatment inhibited TLR9 and NF-κB expression in small intestine of 5-FU- treated mice and pro-inflammatory IL-1β secretion in serum of 5-FU- treated mice. Meanwhile administration of HCQ reduced the number of macrophages in small intestine of 5-FU-treated mice. Then BMDMs were cultured, transfected with CT-DNA and treated with HCQ in vitro. We found HCQ efficiently inhibited TLR9 expression, translocation of NF-κB to nucleus, and IL-1β secretion in supernatant of CT-DNA stimulated BMDMs. Conclusions These results provides a new insight into the mechanism of chemotherapy induced intestinal mucositis and indicate HCQ may be used as a strategy against intestinal mucositis during 5-FU chemotherapy. References Woo S-R, Fuertes MB, Corrales L, et al. STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors. Immunity 2014;41:830–42. Hu B, Jin C, Li H-B, et al. The DNA Sensing Aim2 Inflammasome Controls Radiation Induced Cell death and Tissue Injury. Science (New York, NY). 2016;354:765–8. Miura K, Kodama Y, Inokuchi S, et al. Toll-Like Receptor 9 Promotes Steatohepatitis by Induction of Interleukin-1β in Mice. Gastroenterology. 2010;139:323–34.e7. Acknowledgements The authors confirm that there are no conflicts of interest. Disclosure of Interest None declared.

Neutrophils play a central role in innate immunity and are rapidly recruited to sites of infection and injury. Neutrophil apoptosis is essential for the successful resolution of inflammation. Necrostatin-1 (Nec-1,methyl-thiohydantoin-tryptophan (MTH-Trp)), is a potent and specific inhibitor of necroptosis[1] (a newly identified type of cell death representing a form of programmed necrosis or regulated non apoptotic cell death) by inhibiting the receptor interacting protein 1(RIP1) kinase. Here we report that Nec-1 specifically induces caspase-dependent neutrophils apoptosis and overrides powerful anti-apoptosis signaling from survival factors such as GM-CSF and LPS. We showed that Nec-1 markedly enhanced the resolution of established neutrophil-dependent inflammation in LPS-induced acute lung injury in mice. We also provided evidence that Nec-1 promoted apoptosis by reducing the expression of the anti-apoptotic protein Mcl-1 and increasing the expression of pro-apoptotic protein Bax. Thus, Nec-1 is not only an inhibitor of necroptosis, but also a promoter of apoptosis, of neutrophils, enhancing the resolution of established inflammation by inducing apoptosis of inflammatory cells. Our results suggest that Nec-1 may have potential roles for the treatment of diseases with increased or persistent inflammatory responses.

Four-wheel independent drive electric vehicles (4WID EV) drive safely and stably, which depends on current road conditions, especially road friction coefficient and slope, and different driving control strategies are used according to road conditions. Therefore, a road identification method is proposed to estimate the road information. Firstly, we design a road identification algorithm to identify the current road conditions of 4WID EV, and calculate the optimal slip ratio of the current road surface by curve fitting method. When the wheel slip ratio is controlled near the optimal slip ratio, the wheel adhesion coefficient can be maximized to prevent the wheel from slipping. Then, a slope identification algorithm based on Luenberger state observer is designed to identify the various slopes of uphill and downhill, and it provides a reference for the calculation of the slope compensation torque. Finally, through the joint simulation platform of MATLAB/Simulink and Carsim, it shows that the proposed road identification can identify the current road conditions and slope effectively.

Because dendritic cells (DCs) play critical roles in the pathogenesis of rheumatoid arthritis, modulation of their functions could serve as a novel therapy. In this study, we demonstrated that FTY720 treatment significantly suppressed the incidence and severity of collagen-induced arthritis (CIA) in DBA/1J mice via the modulation of DC functions. In FTY720-treated CIA mice, a decrease in the number of DCs in local draining lymph nodes (LNs) was observed. In vitro, FTY720 inhibited the trafficking of LPS-stimulated bone marrow–derived DCs (BMDCs). Decreased secretion of CCL19 and downregulation of CCR7 on DCs may explain the mechanisms underlying the impairment of DC migration induced by FTY720. In a DC-induced mouse arthritis model, FTY720 treatment also suppressed the incidence and severity of arthritis, which was correlated with a decrease in the migration of injected BMDCs to draining LNs. Although lower levels of costimulatory molecules (CD40, CD80, and CD86) and I-Aq expressed on LN DCs were observed in FTY720-treated mice, in vitro analysis showed no effect of FTY720 on LPS-stimulated BMDC maturation. Furthermore, LN cells from FTY720-treated CIA mice displayed diminished production of proinflammatory cytokines in response to collagen II and Con A stimulation. In addition, the ratio of Th1/Th2 in the draining LNs of mice with DC-induced arthritis was decreased upon FTY720 treatment. This finding was consistent with the fact that FTY720 suppressed IL-12p70 production in cultured BMDCs. Taken together, these results indicate that inhibition of DC migration by FTY720 may provide a novel approach in treating autoimmune diseases such as rheumatoid arthritis.

This study aimed to investigate whether apigenin (API) suppresses arthritis development through the modulation of dendritic cell functions. Bone marrow‐derived dendritic cells (BMDCs) were stimulated in vitro with lipopolysaccharide (LPS) and treated with API for 24 hrs; DC functions, including phenotype expressions, cytokine secretion, phagocytosis and chemotaxis, were then investigated. The effects of API on collagen‐induced arthritis (CIA) were examined in vivo, and purified DCs from the lymph nodes (LNs) of API‐treated CIA mice were analysed for phenotypes and subsets. In in vitro, API efficiently restrained the phenotypic and functional maturation of LPS‐stimulated BMDCs while maintaining phagocytotic capabilities. Moreover, API inhibited the chemotactic responses of LPS‐stimulated BMDCs, which may be related to the depressive effect on chemokine receptor 4 (CXCR4). In in vivo, API treatment delayed the onset and reduced the severity of arthritis in CIA mice, and diminished secretion of pro‐inflammatory cytokines in the serum and supernatants from the LN cells of the CIA mice. Similar to the in vitro findings, the API‐treated mice exhibited reduced expression of co‐stimulatory molecules and major histocompatibility complex II on DCs. Furthermore, API treatment strongly down‐regulated the number of Langerhans cells, but not plasmacytoid DCs (pDCs) in LNs, which may be related to the depressive effect of API on the expression of CXCR4 on DCs of peripheral blood. These data provide new insight into the mechanism of action of API on arthritis and indicate that the inhibition of maturation and migration of DCs by API may contribute to its immunosuppressive effects.