Cellular response to titanium discs coated with polyelectrolyte multilayer films

The purpose of this study was to investigate the effects ofpolyelectrolyte multilayer （PEM） coatings on the biological behavior of titanium （Ti） substrates. Collagen type I/hyaluronic acid （Col/HA） and chitosan/hyaluronic acid （Chi/HA） multilayer PEM coatings were introduced onto Ti substrates using layer-by-layer assembly. Contact angle instruments and quartz crystal microbalance were used for film characterization. The results obtained showed that both Col/HA and Chi/HA surfaces had high hydrophilicity and promoted cell adhesion in MC3T3-E1 pre-osteoblast and human gingival fibroblast cells. In addition, the synthesis of function-related proteins and gene expression levels in both MC3T3-E1 and fibroblast cells was higher for the Col/HA coating compared with the Chi/HA coating, indicating better cellular response to the Col/HA coating.

Cellular Response to Irradiation

To explore the nonlinear activities of the cellular signaling system composed of one transcriptional arm and one protein-interaction arm, we use an irradiation-response module to study the dynamics of stochastic interactions. It is shown that the oscillatory behavior could be described in a unified way when the radiation-derived signal and noise are incorporated.

Trimetazidine and Cellular Response in Cardiopulmonary Bypass

Background: Organic cellular inflammatory response constitutes a pathophysiological mechanism present in all Coronary Artery Bypass Graftings (CABGs). In this aspect, the organism brings forth its defenses through answers that involve cellular components. Objectives: To evaluate, in a randomized double-blind prospective study, controlled with placebo, the effects of trimetazidine (Tmz) on cellular response, analyzed through the variation of leukocytes, neutrophils and monocytes. Patients and Method: 30 patients were randomly selected to be studied, with no more than a mild ventricular dysfunction, and divided into two groups (Tmz and placebo) stratified by echocardiography and receiving medication/placebo in a 60 mg/day dose. The samples of leukocytes, neutrophils and monocytes were obtained in the pre-operatory day without medication, at surgery day with 12 to 15 days of medication/placebo, with 5 minutes after the aortic declamping, and within 12, 24 and 48 hours after surgery. Results: The leukocytes and neutrophils levels have decreased significantly in the treated group when compared to the control group, in all analyzed moments (p = 0.012;p = 0.005). Conclusions and Clinical Implications: Trimetazidine has proved to reduce significantly the levels of total leukocytes and neutrophils in patients submitted to CABG.

An overview of substrate stiffness guided cellular response and its applications in tissue regeneration

Cell-matrix interactions play a critical role in tissue repair and regeneration.With gradual uncovering of substrate mechanical characteristics that can affect cell-matrix interactions,much progress has been made to unravel substrate stiffness-mediated cellular response as well as its underlying mechanisms.Yet,as a part of cell-matrix interaction biology,this field remains in its infancy,and the detailed molecular mechanisms are still elusive regarding scaffold-modulated tissue regeneration.This review provides an overview of recent progress in the area of the substrate stiffness-mediated cellular responses,including 1)the physical determination of substrate stiffness on cell fate and tissue development;2)the current exploited approaches to manipulate the stiffness of scaffolds;3)the progress of recent researches to reveal the role of substrate stiffness in cellular responses in some representative tissue-engineered regeneration varying from stiff tissue to soft tissue.This article aims to provide an up-to-date overview of cell mechanobiology research in substrate stiffness mediated cellular response and tissue regeneration with insightful information to facilitate interdisciplinary knowledge transfer and enable the establishment of prognostic markers for the design of suitable biomaterials.

Comparison of cellular responses across multiple passage numbers in Ba/F3-BCR-ABL cells induced by silver nanoparticles

With the rapid development of nanotechnology and increasingly broad bio-application of engineered nanomaterials, their bio- hazards have become a serious public concern. It is believed that the chemical nature, particle size, morphology, and surface chemistry of nanomaterials are key parameters that influence their toxicity. Although cultured ceils have been widely used to evaluate nanomaterial toxicity, it remains unclear whether the passage of these cells affects the evaluation results. In the pre- sent study, Ba/F3 cells transfected with the BCR-ABL gene were subcultured to study the effect of passage number on cell sta- bility and their cellular responses upon exposure to nanomaterials. The results demonstrated that proliferation, cellular senes- cence, BCR-ABL gene expression, cell cycle and apoptosis were stable across multiple passages. Senescence and BCR-ABL gene expression of cells from different passage cells were unchanged when treated with silver nanoparticles （AgNPs）. In addi- tion, the cells at multiple passage numbers were all arrested in the G2/M phase and apoptosis was induced by the AgNPs. These nanoparticles could enter cells via endocytosis and localize in the cndosomes, which were also not influenced by passage number. These data suggest that short-term passage would not affect cultured cell stability and toxicity assessment using these cells would be consistent when maintained appropriately.

Proteomic analysis on cellular response induced by nanoparticles reveals the nano-trafficking pathway through epithelium

The application of nanomedicines in oral drug delivery effectively promotes the drug absorption and transportation through enterocytes.Nevertheless,the absence of mechanism studies on efficacy and safety limits their final translation in humans.Although the vesicular trafficking has been verified as the general character for transport of nanomedicines,the deeper mechanism in molecular mechanism is still unclear.Moreover,the cellular transport of nanomedicines is a dynamic process involved by different organelles and components.However,most of existing studies just pay attention to the static location of nanomedicines,but neglect the dynamic biological effects on cells caused by them.Here,we prepared gold nanoparticles(Au NPs)as the model and cultured epithelial cell monolayer to explore the nano-bio interactions at the molecular level.The traditional pharmacological inhibition strategy and subcellular imaging technology elucidated the macropinocytosis/endosome/MVB/lysosome pathway during the transportation of Au NPs.Proteomics strategy based on mass spectrometry(MS)was utilized to identify and quantify proteins involved in the cellular transport of nanomedicines.Multiple proteins related to subcellular structure,signal transduction,energy transformation and metabolism regulation were demonstrated to be regulated by nanoparticle transport.These alterations of protein expression clarified the effects of intracellular proteins and verified the conventional findings.More importantly,it revealed a feedback mechanism of cells to the nano-trafficking.We believed that these new regulatory mechanisms provided new insights into the efficient transport of nanomedicines through epithelial barriers.

Cellular responses to nanoscale substrate topography of TiO_(2) nanotube arrays: cell morphology and adhesion

Nanotopographical features can be beneficial in augmenting cell functions and increasing osteogenic potential.However,the relationships between surface topographies and biological responses are difficult to establish due to the difficulty in controlling the surface topographical features at a low-nanometre scale.Herein,we report the fabrication of well-defined controllable titanium dioxide(TiO_(2))nanotube arrays with a wide range of pore sizes,30-175 nm in diameter,and use of the electrochemical anodization method to assess the effect of surface nanotopographies on cell morphology and adhesion.The results show that TiO_(2) nanotube arrays with pore sizes of 30 and 80 nm allowed for cell spreading of bone marrow-derived mesenchymal stem cells with increased cell area coverage.Additionally,cell adhesion was significantly enhanced by controlled nanotopographies of TiO_(2) nanotube arrays with 80 nm pore size.Our results demonstrate that surface modification at the nano-scale level with size tunability under controlled chemical/physical properties and culture conditions can greatly impact cell responses.These findings point to a new direction of material design for bone-tissue engineering in orthopaedic applications.

Expression patterns and action analysis of genes associated with physiological responses during rat liver regeneration:Cellular immune response

AIM： To study the cellular immune response during rat liver regeneration （LR） at a transcriptional level. METHODS： Genes associated with the cellular immune response were obtained by collecting the data from databases and retrieving articles. Gene expression changes during LR were detected by rat genome 230 2.0 array. RESULTS： A total of 127 genes were found to be associated with LR. The number of initially and totally expressing genes in the initial phase of LR [0.5-4 h after partial hepatectomy （PH）], transition from Go-G, （4-6 h after PH）, cell proliferation （6-66 h after PH）, cell differentiation and structure-function reconstruction （66-168 h after PH） was 54, 11, 34, 3 and 54, 49, 70, 49 respectively, illustrating that the associated genes were mainly triggered at the initiation of LR, and worked at different phases. According to their expression similarity, these genes were classified into 41 up-regulated, 21 predominantly up-regulated, 41 down-regulated, 14 predominantly down-regulated, 10 similarly up-regulated and down-regulated genes, respectively. The total up- and down-regulated expression times were 419 and 274, respectively, demonstrating that the expression of most genes was increased while the expression of a small number of genes was decreased. Their time relevance was classified into 14 groups, showing that the cellular physiological and biochemical activities were staggered during LR. According to the gene expression patterns, they were classified into 21 types, showing the activities were diverse and complicated during LR.CONCLUSION： Antigen processing and presentation are enhanced mainly in the forepart, prophase and anaphase of LR. T-cell activation and antigen elimination are enhanced mainly in the forepart and prophase of LR. A total of 127 genes associated with LR play an important role in cellular immunity.

Changes in cellular proliferation and plasma products are associated with liver failure

AIM To study the differences in immune response and cytokine profile between acute liver failure and selflimited acute hepatitis.METHODS Forty-six patients with self-limited acute hepatitis(AH), sixteen patients with acute liver failure(ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced selflimited AH and ALF. Thus, we worked with five groups: Hepatitis A virus(HAV)-induced self-limited acute hepatitis(HAV-AH), HAV-induced ALF(HAV-ALF), nonviral-induced self-limited acute hepatitis(non-viral AH), non-viral-induced acute liver failure(non-viral ALF), and healthy subjects(HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.RESULTS The levels of mitochondrial DNA(mt DNA) and the cytokines investigated [interleukin(IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology(P < 0.05). High plasma mt DNA and IL-10 were the best markers associated with ALF [mt DNA: OR = 320.5(95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8(95%CI: 1.38-257.94), P = 0.028] and death [mt DNA: OR = 12.1(95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01(95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NK^(bright), NKT and regulatory T cells(TReg) predominated in virusspecific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION mt DNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.

Hypothalamic circuits and aging:keeping the circadian clock updated

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice

As of December 2022,2603 laboratory-identified Middle East respiratory syndrome coronavirus(MERS-CoV)infections and 935 associated deaths,with a mortality rate of 36%,had been reported to the World Health Organization(WHO).However,there are still no vaccines for MERS-CoV,which makes the prevention and control of MERS-CoV difficult.In this study,we generated two DNA vaccine candidates by integrating MERS-CoV Spike(S)gene into a replicating Vaccinia Tian Tan(VTT)vector.Compared to homologous immunization with either vaccine,mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses.The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012,England1 and KNIH strains of MERS-CoV.Prime-Boost immunization also induced strong MERS-S specific T cells responses,with high memory and poly-functional(CD107a-IFN-γ-TNF-α)effector CD8t T cells.In conclusion,the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S.This study not only provides a promising set of MERS-CoV vaccine candidates,but also proposes a heterologous sequential immunization strategy worthy of further development.

The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection

This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.

Cortical spreading depression-induced preconditioning in the brain

Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the underlying mechanism for this phenomenon remains relatively unclear. To date, numerous issues exist regarding the experimental model used to precondition the brain with cortical spreading depression, such as the administration route, concentration of potassium chloride, induction time, duration of the protection provided by the treatment, the regional distribution of the protective effect, and the types of neurons responsible for the greater tolerance. In this review, we focus on the mechanisms underlying cor- tical spreading depression-induced tolerance in the brain, considering excitatory neurotransmission and metabolism, nitric oxide, genomic reprogramming, inflammation, neurotropic factors, and cellular stress response. Specifically, we clarify the procedures and detailed information regarding cortical spreading depression-induced preconditioning and build a foundation for more comprehensive investigations in the field of neural regeneration and clinical application in the future.

Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno-carrier

AIM: To develop hepatitis C virus (HCV) vaccine using HBcAg as the immuno-carrier to express HCV T epitope and to investigate its immunogenicity in mice. METHODS: We constructed the plasmid pTrc-coreNheI using gene engineering technique, constructed the pcDNA3.1-coreNheI-GFP plasmid with GFP as the reporter gene, and transfected them into Hela cells. The expression of GFP was observed under confocal microscopy and the feasibility of using HBcAg as an immuno-carrier vaccine was studied. pTrc-core gene with a synthetic T epitope antigen gene of HCV (35-44aa) was fused and expressed in the plasmid pTrc- core-HCV (T). For the fusion of the HBcAg-T protein, sucrose, density gradient centrifugation was used, and its molecular weight and purity were analyzed by SDS- PAGE. Then balb/c mice were immunized by the plasmid with the HBcAg (expressed by pTrc-core) protein as control. The tumor regression potential was investigated in mice and evaluated at appropriate time. After three times of immunization, the peripheral blood and spleen of vaccinated mice were collected. HBcAb was detected by ELISA, and nonspecific T lymphocyte proliferation and response of splenocytes were respectively examined by MTT assay. T cell subset of blood and spleen were detected by FACS. RESULTS: GFP was successfully expressed. Tumor regression trial showed that no tumor formation was found in the group receiving immunization, while tumor xenograft progression was not changed in the control group. Strong nonspecific lymphocyte proliferation response was induced. FACS also showed that the ratio of CD8+ T cells in the experimental group was higher than the controls, but the serum HBcAb in experimental group was similar to the control. CONCLUSION: HBcAg can be used as an immuno-carrier of vaccine, the fusion of HBcAg-T protein could induce stronger cellular immune responses and it might be a candidate for therapeutic vaccines specific for HCV.

Heat shock cognate 71 (HSC71) regulates cellular antiviral response by impairing formation of VISA aggregates

In response to viral infection, RIG-I-like RNA helicases detect viral RNA and signal through the mitochondrial adapter protein VISA. VISA activation leads to rapid activation of transcription factors IRF3 and NF-κB, which collaborate to induce transcription of type I interferon (IFN) genes and cellular antiviral response. It has been demonstrated that VISA is activated by forming prion-like aggregates. However, how this process is regulated remains unknown. Here we show that overexpression of HSC71 resulted in potent inhibition of virus-triggered transcription of IFNB1 gene and cellular antiviral response. Consistently, knockdown of HSC71 had opposite effects. HSC71 interacted with VISA, and negatively regulated virus-triggered VISA aggregation. These findings suggest that HSC71 functions as a check against VISA-mediated antiviral response.

Immunogenicity of the Spike Glycoprotein of Bat SARS-like Coronavirus

A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γand IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.

The histone acetyltransferase MOF is required for the cellular stress response

When exposing to environmental stress or internal damage, such as genotoxic stress, oxidative stress, and heat stress, cells produce a series of adaptive responses called cellular stress responses. The major proteins involved in cellular stress are heat shock proteins （HSPs）.

Influence of Photoperiod over Morphometric and Hematological Parameters of Juvenile Piracanjubas （Brycon orbygnianus）

The aim of this study was to evaluate morphometric and hematological parameters of juveniles Piracanjubas treated with two distinct photoperiod. Twenty nine fish with 100 g, in a factorial design were performed in 18 h light：6 h dark （18L：6D） and 6L：lSD two different photoperiod, and morphometric and hematological parameters were evaluated at 45 d and 90 d after photoperiod treatment. Benzocaine 1% was used for euthanasia. Fish were weighed and measured, so as visceral fat, liver and gonads. Hematocrit, total count of white cells, lymphocytes and neutrophils were counted. Results showed that there was no significant relationship between bodyweight and standard length. Significant interaction （P = 0.00018） had been found between the fat index （FI） and gonado-somatic index （GSI） and the photoperiod and time. At 90 d, the fish kept in 18L：6D had a lower rate of fat than the fish kept in 6L：18D （P 〈 0.05）. The GSI was higher in the group 6L.＇18D compared with the 18L：6D （P 〈 0.005）. There was no interaction between photoperiod and period of treatment for total leukocyte count, however with 90 d, the total leukocyte count was decreased （P 〈 0.05）. Moreover, decrease of the hematocrit from 58.1% to 46.9% and an increase of lymphocytes from 31.5% to 43.5% had been found in fish kept in 18L：6D after 90 d （P 〈 0.05）. Fish kept in 6L：ISD presented an increase in segmented neutrophils and lymphocytes （P 〈 0.05）. It is concluded that photoperiod maintained at 6L： 18D for Piracanjubas permits a greater gonadal development and an amount of immune cells over the photoperiod maintained in 18L： 6D.

In vitro investigation of cellular effects of magnesium and magnesium-calcium alloy corrosion products on skeletal muscle regeneration

Biodegradable magnesium(Mg)has garnered attention for its use in orthopaedic implants due to mechanical properties that closely match to those of bone.Studies have been undertaken to understand the corrosion behaviour of these materials and their effects on bone forming cells.However,there is lack of research on how the corrosion of these biomaterials affect surrounding tissues such as skeletal muscle.Mg plays an important role in the structural and functional properties of skeletal muscle.It is therefore important to investigate the response of skeletal muscle cells to both soluble(Mg ions)and insoluble(corrosion granules)corrosion products.Through in vitro studies it is possible to observe the effects of corrosion products on myotube formation by the fusion of single muscle precursor cells known as myoblasts.To achieve this goal,it is important to determine if these corrosion products are toxic to myotubes.Here it was noted that although there was a slight decrement in cellular viability after initial exposure,this soon recovered to control levels.A high Ca/Mg ratio resulted in the formation of large myotubes and a low Ca/Mg ratio negatively affected myotube maturation.Mg^2+and Ca^2+ions are important in the process of myogenesis,and the concentration of these ions and the ratio of the ions to each other played a significant role in myotube cellular activity.The outcomes of this study could pave the way to a bio-informed and integrated approach to the design and engineering of Mg-based orthopaedic implants.

Immunosuppressive therapy selectively modulates B-cell responses in patients with rheumatic and musculoskeletal diseases receiving the inactivated COVID-19 vaccine

Background:Immunosuppressive medication reduces the immunogenicity of the coronavirus disease 2019(COVID-19)vaccines in patients with rheumatic and musculoskeletal diseases(RMDs).However,the underlying mechanism remains unclear.The primary aim of our study was to dissect the impact of immunosuppressive medication on cellular and humoral immune responses in RMD patients receiving the inactivated COVID-19 vaccine.Methods:A total of 28 RMD patients and five healthy controls(HCs)receiving two doses of the inactivated COVID-19 vaccine(Sinovac-CoronaVac)were prospectively enrolled.Blood samples were collected before the primary vaccination(Week 0)and one week after the second vaccination(Week 5).Neutralizing antibody(nAb)titers and autoantibody titers were measured by a pseudovirus-based neutralization assay and enzyme-linked immunosorbent assay,respectively.CD4^(+)T-cell and CD19^(+)B-cell subsets and serum cytokines were analyzed by flow cytometry.Results:The inactivated COVID-19 vaccine was immunogenic in RMD patients and HCs after the second vaccination,but the nAb titers were lower in RMD patients than those in HCs.Only patients with systemic lupus erythematosus(SLE)had notably increased nAb titers.Remarkably,IgG^(+)CD27^(+),IgG^(+)IgG1^(+),and IgG^(+)IgG1^(−)B cells were reduced,whereas IgG−IgG1^(+)B cells,and total IgA and IgG titers were markedly increased.However,Tfh cell and Tfr cell subsets and cytokines produced by Tfh cells were not increased.The flare rate was low in RMD patients with comparable autoantibody titers,unchanged CD4^(+)T cell subsets and serum proinflammatory cytokines(interleukin[IL]-6,IL-17,interferon-γ,and tumor necrosis factor-α)after the second vaccination.Conclusions:Immunosuppressive therapy decreased the immunogenicity of the vaccine and maintained a low flare rate by selectively modulating B cell but not CD4^(+)T cell responses in RMD patients receiving the inactivated COVID-19 vaccine.Optimization of the treatment regimen might ensure a durable and robust COVID-19 vaccination response.