Sjögren’s disease (SjD) is a chronic autoimmune disease featured by lymphocytic infiltration of exocrine glands and numerous organ involvements, but central nervous system involvement is relatively rare. Due to the variety of symptoms, diagnosis is particularly difficult under certain conditions, which may delay the optimal timing of treatment. Increased clinical awareness and effective pharmacotherapies are urgently needed. A case of a 39-year-old female was initially considered to have an intracranial occupancy based upon rapidly progressing nervous symptoms including intermittent fever, parieto-occipital headache, numbness and weakness in the hand, blurred vision, memory impairment and imaging findings, but it was ultimately clarified that she had SjD involving nervous system, with immunological results showing positive antinuclear antibodies (1:640) and anti-SSA/SSB antibodies (+++) in serum and pathological findings suggesting vasculitis of brain. Finally, she was successfully treated with rituximab. The onset of SjD may even only manifest as neurological symptoms, which could be easily confused with other systemic or neurological diseases, thus demanding careful differential diagnosis through a detailed medical history and immunological, even pathological examinations to clarify the etiology. Rituximab is an effective treatment option for SjD involving nervous systems, which is an option not commonly featured in standard treatment protocols.

This study aimed to evaluate the efficacy and safety of upadacitinib in patients with refractory Behcet’s syndrome (BS). A multicentre, single-arm trial was conducted from February 2023 to August 2025. Eligible patients had BS refractory to at least two immunosuppressive agents or one targeted therapy for a minimum of 6 months. Participants discontinued previous targeted therapies and received upadacitinib 15 mg/day for up to 48 weeks, in addition to their ongoing glucocorticoid and immunosuppressant regimens. Clinical features, inflammatory markers, imaging findings, and treatment data were collected throughout follow-up. The primary endpoint was the overall response rate (ORR; complete response [CR] plus partial response [PR]) at 24 weeks. Twenty-seven patients (16 male; median age 36 years) were enrolled, with a median baseline BDCAF score of 4 (range: 2–7). Affected systems included the mucocutaneous, articular, gastrointestinal, cardiovascular, and ocular systems. The ORR at 24 weeks was 85.2

Cerebral malaria (CM) is a severe complication of Plasmodium infection, classically attributed to parasite sequestration and neuroinflammation. Here, we uncover a spleen-centered humoral autoimmune circuit that drives CM pathology. Proteomic analyses identify CD36 as a dominant host-derived antigen enriched in infected red blood cells (iRBCs), triggering anti-CD36 autoantibody production in patients with falciparum malaria. Although contributing to iRBCs clearance, these autoantibodies also target other CD36-expressing cells, thereby driving thrombocytopenia, endothelial injury, and macrophage activation, ultimately amplifying systemic inflammation. Mechanistically, Plasmodium infection recruits Ly6c+Glut1hi macrophages to the spleen through the CCL2-CCR2 axis. These macrophages exhibit elevated proteasome activity and drive B cell activation and anti-CD36 antibody production. Targeting Ly6c+Glut1hi macrophages, we develop Glutoborin, a GLUT1-directed proteasome inhibitor that preferentially suppresses their function, reduces autoantibody production, and alleviates CM-associated pathology in vivo. Together, these findings establish a spleen-centered anti-CD36 autoimmune circuit as a key driver of CM and nominate Ly6c+Glut1hi macrophages as therapeutic targets.

Objective Behçet syndrome (BS) is a systemic autoimmune vasculitis characterized by immune dysregulation involving multiple immune cell subsets. CD161+ Treg cells exhibit proinflammatory properties and impair immune regulation during inflammation. This study aimed to investigate the alterations in CD161+ Treg cells in BS and their clinical relevance, particularly in disease pathogenesis and neurologic involvement. Methods This prospective multicenter study included 182 patients diagnosed with BS at the three hospitals between 2018 and 2024, 166 patients with systemic lupus erythematosus (SLE) and 149 patients with rheumatoid arthritis (RA) and 114 patients with healthy controls (HCs). Demographic and clinical data were recorded. CD4+CD25highCD127lowCD161+ T cells (CD161+ Treg cells) in peripheral blood were analyzed via flow cytometry. Statistical analysis included the Wilcoxon rank‐sum test, Fisher's exact test, and logistic regression, with P < 0.05 considered significant. Results Patients with BS had a significantly higher proportion among total Treg cells and CD4+ T cells, as well as higher absolute number of CD161+ Treg cells compared to HCs. CD161+ Treg cell levels negatively correlated with Foxp3+ Treg cells and positively correlated with Teff cells. Patients with BS had higher absolute number of CD161+ Treg cells than that in patients with SLE and in patients with RA. Moreover, patients with BS with higher erythrocyte sedimentation rate or C‐reactive protein or with neurologic involvement exhibited higher CD161+ Treg cells, which were identified as a risk factor for neurologic involvement. Among 41 patients with BS observed after treatment, CD161+ Treg cells significantly decreased, correlating with reduced disease activity. Conclusion Patients with BS exhibit an increased CD161+ Treg cells in peripheral blood, which may contribute to immune dysregulation and neurologic involvement. The reduction of CD161+ Treg cells following treatment suggests their potential role as a biomarker for disease activity in BS.

Systemic lupus erythematosus (SLE) has a complex, multifactorial etiology, which contributes to a lack of definitive cure and limited treatment efficacy. Here, we report that cyclic GMP-AMP synthase (cGAS) is significantly activated in SLE patients. We further demonstrate that cGAS deletion protects mice from lupus-like symptoms induced by the TLR7 agonist imiquimod (IMQ). In a screen of 3,159 FDA-approved drugs, we identify the antiplatelet agent prasugrel as a potent cGAS inhibitor. Mechanistically, prasugrel disrupts the DNA-triggered liquid phase condensation and activation of cGAS via direct acetylation. Strikingly, we find that prasugrel exhibits remarkable efficacy in treating SLE in both mouse models and patient cells. Importantly, we report elevated plasma cyclic GMP-AMP (cGAMP) in SLE patients and identify it as a potential biomarker for predicting prasugrel response. Thus, our work elucidates the essential role of cGAS in SLE pathogenesis and presents prasugrel as a promising therapeutic option with immediate translational potential.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and progressive joint destruction driven by macrophage polarization and osteoclast activation. Current therapies lack lesion-specificity and cause systemic side effects, highlighting the need for targeted treatment strategies. Here, we developed carrier-free myricetin-arginine conjugate nanozymes (MANZs) via a Mannich reaction-mediated conjugation of l-arginine and myricetin, followed by self-assembly driven by noncovalent interaction. The MANZs selectively target M1 macrophages via cationic amino acid transporter 2 (CAT2)-mediated uptake, facilitating preferential accumulation in inflamed joints. MANZs exert multi-modal therapeutic effects by scavenging reactive oxygen species (ROS), repolarizing M1 macrophages, and inhibiting osteoclast differentiation. In a collagen-induced arthritis (CIA) mouse model, MANZs significantly alleviated joint swelling, synovitis, and bone erosion without systemic toxicity. This work establishes a promising paradigm for RA therapy by integrating cationic amino acids with natural polyphenols into a self-assembled, target-specific nanoplatform with high biocompatibility and translational potential.

Background SLE complicated with thrombotic thrombocytopenic purpura (SLE-TTP) is a rare but potentially fatal condition. Current studies regarding SLE-TTP are limited to case reports and literature reviews. This study presents a cohort of patients with SLE-TTP and aims to investigate their clinical characteristics and treatment outcomes, as well as to explore the efficacy of rituximab (RTX) maintenance therapy (RMT) for relapse prevention and long-term disease control.Methods Patients with SLE-TTP were retrospectively identified in an SLE cohort. Baseline characteristics, acute-phase treatment responses and long-term outcomes were collected. All patients received RTX-containing induction therapy during the acute phase of TTP. Maintenance therapy was categorised as RMT (regular RTX infusions) or non-RMT (conventional immunosuppressants and/or biologics) regimens. TTP relapse, lupus low disease activity state (LLDAS) and infection rates were compared between groups.Results Of 33 patients with SLE-TTP, 31 (94%) achieved clinical remission following RTX-containing induction therapy, while 2 died during the acute phase. Fourteen patients (45%) received RMT, and 17 (55%) received non-RMT regimens. During a median follow-up of 22.9 months, TTP relapse occurred in seven (23%) patients: one (7%) in the RMT group and six (35%) in the non-RMT group. Kaplan-Meier analysis revealed significantly longer relapse-free survival with RMT (log-rank p=0.027). All patients receiving RMT achieved LLDAS, compared with 59% of patients in the non-RMT group. Infection rates were comparable between the two groups.Conclusions RTX-containing induction regimens resulted in high rates of clinical remission in patients with SLE-TTP. RMT was associated with a significantly reduced risk of TTP relapse and superior long-term control of SLE disease activity, without an excess risk of severe infection. These findings support RMT as a potential option for long-term management of SLE-TTP.

OBJECTIVE:To evaluate the efficacy, safety and immunological effects of tofacitinib in patients with Sjögren's disease (SjD), focusing on its impact on disease activity and immune cell modulation. METHODS:Two independent cohort studies, one retrospective (Cohort I) and one prospective (Cohort II), were conducted to investigate the efficacy of oral tofacitinib treatment in patients diagnosed with SjD. All participants were evaluated for changes in disease activity and lab parameters. Circulating T cells were analysed, focusing on follicular helper T (Tfh) cells and peripheral helper T (Tph) cells. RESULTS:In cohort I, 112 patients treated with tofacitinib showed a significant improvement in the ESSDAI score [median (IQR), 8.00 (4.25, 15.75) vs 6.50 (2.25, 12.75), P < 0.001]. In cohort II, ten patients completed the 12-month treatment period. There was a significant reduction in ESSDAI scores at the sixth month compared with baseline (P = 0.001). In total, 80% (8/10) of patients achieved a decrease of at least one point or 15% in ESSPRI scores. A significant reduction in the proportion of Th17 cells was observed (mean ± SD, 14.84 ± 7.70 vs 7.74 ± 4.24, P = 0.008). A decrease in Tfh and Tph cells was also observed, along with decreased pSTAT-3 levels in CD4+ T cells and disease activity scores. No serious adverse events were observed in the two cohorts. CONCLUSIONS:Tofacitinib effectively improves disease activity and immune regulation in SjD, and it is associated with suppressing Tfh and Tph cells, suggesting its potential as a treatment option. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT05087589.

OBJECTIVE:To systematically investigate the rheumatic disease spectrum associated with anti-PM/Scl antibodies and to clarify their clinical significance in idiopathic inflammatory myopathies (IIM). METHODS:Patients who were tested positive for anti-PM/Scl antibodies by immunoblotting at Peking University People' s Hospital from January 2016 to December 2024 were enrolled. Clinical and immunolo gical data were systematically collected and compared across the subgroups defined by anti-PM/Scl75, anti-PM/Scl100, or dual antibody positivity. RESULTS:A total of 422 anti-PM/Scl-positive patients were enrolled. Among them, 83.2% (351/422) were diagnosed with connective tissue disease (CTD), 7.8% (33/422) were not diagnosed with CTD, and 9.0% (38/422) had an undetermined clinical diagnosis. Among 422 patients, most commonly represented by IIM (19.7%), systemic sclerosis (SSc, 14.2%), overlap syndrome (11.8%), undifferentiated CTD (UCTD, 10.4%), rheumatoid arthritis (6.9%), Sjögren syndrome (6.4%), and systemic lupus erythematosus (6.2%), the remaining diseases accounting for 24.4%. Within the IIM subgroup, dermatomyositis predominated (74.7%), followed next by anti-synthetase syndrome (21.7%) and immune-mediated necrotizing myopathy (3.6%). Anti-PM/Scl75 antibodies were detected in 52.1% (220/422) of the total patients, anti-PM/Scl100 in 43.6% (184/422), and both in 4.3% (18/422). In the subsequent detailed analysis of the anti-PM/ Scl-positive subgroup, double-positive patients showed a significantly higher prevalence of SSc (38.9% vs. 14.1% vs. 12.0%, P=0.015) and interstitial lung disease (ILD, 70.6% vs. 28.8% vs. 35.4%, P=0.002) than those individuals with single antibody positivity alone. Raynaud phenomenon was observed more frequently in both the double-positive and anti-PM/Scl75-positive groups than in the anti-PM/Scl100-positive group (29.4% vs. 21.3% vs. 10.9%, P=0.007). The measured proportion of peri-pheral CD8+ T cells was also higher in double-positive patients (35.9%±14.1% vs. 30.4%±11.2% vs. 26.5%±9.7%, P= 0.008), whereas absolute regulatory T-cell levels were lower in the anti-PM/Scl75-positive group compared directly with the anti-PM/Scl100-positive group [7.6% (5.4%, 10.9%) vs. 9.0% (7.9%, 12.0%) vs. 8.8% (5.2%, 9.7%), P=0.017]. Additionally, co-positivity for anti-PM/Scl and other myositis- specific or myositis-associated antibodies was strongly associated with an increased frequency of ILD (P < 0.05). CONCLUSION:Anti-PM/Scl antibodies define a broad disease spectrum encompassing IIM, SSc, overlap syndromes, and UCTD. Dual positivity for anti-PM/Scl75 and anti-PM/Scl100 identifies patients prone to systemic sclerosis and pulmonary involvement, suggesting additive pathogenic effects of the two antibody specificities.

OBJECTIVE:This study aimed to assess the efficacy and safety of baricitinib in Takayasu arteritis (TAK) refractory to TNF-α inhibitors. METHODS:We conducted a multicentre, single-arm trial between February 2021 and August 2023. Patients with TAK unresponsive to at least 6 months of TNF-α inhibitors were treated with baricitinib 4 mg daily for up to 48 weeks, while continuing of immunosuppressants and glucocorticoids. Clinical features, inflammatory parameters, imaging changes and treatment data were collected during follow-up. The primary end point was the overall response (ORR) (complete response [CR] plus partial response [PR]) at 24 weeks. RESULTS:A total of 10 patients (nine female and one male) patients were enrolled, with median age of 29 years (26.0, 35.3) and a median disease duration of 56.5 months (31.8, 88.5). The ORR at 24 weeks was 80%, with six patients achieving CR and two achieving PR. Disease progression was noted in the remaining two patients. Disease activity, ESR and CRP at 24 weeks were significantly decreased compared with those at baseline. The median glucocorticoid dosage decreased from 20.0 mg/day (15.0, 26.3) at baseline (P < 0.001) to 6.3 mg/day (4.4, 10.6) at 24 weeks. No relapse was observed in the eight patients who achieved a response. The adverse effects (AEs) included upper respiratory tract infection (n = 2) and diarrhoea (n = 1), with no serious AEs reported. CONCLUSION:Baricitinib is effective in patients with TAK resistant to conventional treatments and anti-TNF-α therapy and demonstrates a notable steroid-sparing effect. TRIAL REGISTRATION:ClinicalTrials.gov; NCT06662721.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease associated with psoriasis (PsO), characterized by complex clinical manifestations, a protracted course, and a propensity for relapses. However, in China, there is a notable deficiency in the recognition and early diagnosis of PsA, with missed or incorrect diagnoses being relatively common. Therefore, this consensus aims to promote early diagnosis and optimise outcomes of patients with PsA. Methods: This consensus was developed by the Expert Consensus Research Group on Early Recognition, Diagnosis, and Treatment of PsA, the Psoriatic Arthritis Group of the Committee of Rheumatology and Immunology, Cross-Strait Medical and Health Exchange Association. The process involved collecting clinical questions through online questionnaires, followed by rounds of expert meetings and revisions. The evidence was systematically reviewed from databases such as PubMed, Embase, Web of Science, Cochrane Library, and Chinese databases, with the evidence quality and recommendation strength graded according to the 2011 Oxford Centre for Evidence-Based Medicine levels. Results: We distributed online questionnaires to the expert panel involved in the three rounds of surveys. At the end of the third round of surveys, four overarching principles and sixteen recommendations were collected. The level of agreement with these recommendations ranged from 83.33% to 100%. Consensus was reached on all 16 clinical recommendations identified by the Committee (i.e., >= 75% of respondents strongly agreed or agreed), and specific recommendations were formulated for the risk assessment and early screening of PsA, as well as the early treatment and management of PsA. Conclusion: This consensus provides scientific evidence and guidance for the early recognition, diagnosis, and treatment of PsA, which is expected to raise clinical physicians' awareness of PsA, reduce misdiagnosis, and improve patients' quality of life and prognosis.

OBJECTIVES:The objective of this study was to evaluate the efficacy and safety of tofacitinib in the treatment of active dermatomyositis (DM) and anti-synthetase syndrome (ASS). METHODS:Tofacitinib was administered at a dose of 5 mg twice daily to patients who exhibited inadequate response to conventional treatments. The primary end point was the reduction in T follicular helper (Tfh) cells at week 24. Key secondary end points included clinical scores. Moreover, we analysed the immunological profiles and conducted RNA sequencing (RNAseq) on peripheral blood samples from four patients. RESULTS:A total of 26 patients were enrolled, with 21 completing the study. Both DM and ASS patients demonstrated significant improvements in disease activity. Among these patients, the percentage of Tfh cells in peripheral blood decreased in 81.0% (17/21) of them (P = 0.003). Significant reductions in Th17 cells were observed in vivo in the peripheral blood mononuclear cells (PBMCs) of these patients (P = 0.017). In vitro, Tfh cells (2.88 ± 1.13 vs 2.28 ± 0.92, P< 0.001), Th17 cells (1.42 ± 0.92 vs 1.01 ± 0.74, P = 0.016), Treg cells (2.06 ± 1.26 vs 0.98 ± 0.65, P = 0.019) and Tfh17 cells (33.38 ± 15.14 vs 30.28 ± 4.89, P = 0.014) were inhibited. RNAseq analysis revealed significant downregulation of genes associated with the 'herpes simplex virus 1 infection' and 'IL-17 signalling' pathway. Myositis Disease Activity Assessment Tool (MDAAT) scores improved in 21 out of 24 patients. Fifteen (62.5%) patients met the criteria for International Myositis Assessment and Clinical Studies (IMACS) definition of improvement (DOI). Importantly, no severe adverse events necessitated treatment discontinuation. CONCLUSION:Tofacitinib demonstrated significant immunologic and clinical effectiveness in DM and ASS patients, reducing key immune cell populations and downregulating immune activation pathways.

Background Nearly 50% of patients with rheumatoid arthritis (RA) fail to respond adequately to current therapies within a clinically effective timeframe. Previous studies have demonstrated that berberine (BBR) exerts therapeutic effects in RA, however, neither its targets nor associated mechanisms have been investigated. Purpose To identify the direct BBR target and elucidate its molecular mechanism in RA. Methods The BBR effects on autophagy and protein citrullination were evaluated using MH7A cells and rats with adjuvant-induced arthritis (AA). Network pharmacology was employed to predict potential BBR target genes in RA. Molecular docking, cellular thermal shift assay (CETSA), solvent-induced protein precipitation (SIP), and surface plasmon resonance (SPR) were conducted to confirm target binding. Western blotting, transmission electron microscopy, immunofluorescence co-localization, chromatin immunoprecipitation (ChIP), dual-luciferase reporter assays, and qRT-PCR were performed to investigate the molecular pathways involved. Results BBR reduced citrullinated protein levels by suppressing autophagy in MH7A cells. Network pharmacology suggested STAT3 as a potential BBR target. Molecular docking, CETSA, SIP, and SPR confirmed binding between BBR and STAT3. In AA rats, BBR treatment significantly lowered serum ACPA levels and decreased the levels of cVIM, citH3, p-STAT3, PAD4, and autophagy markers in AA-FLSs. Mechanistic studies show that STAT3 might directly binds to the PADI4 promoter, promoting its transcription. STAT3 activation or overexpression prevented PAD4 inhibition by BBR, impaired its regulation of p-mTOR, and enhanced autophagy and protein citrullination. On the other hand, PAD4 inhibition enhanced the suppressive effects of BBR on PAD4, autophagy, and protein citrullination without affecting p-STAT3 levels. Conclusions This study demonstrates that BBR alleviates RA and reduces citrullinated protein production by inhibiting autophagy through STAT3/PAD4 pathway. These findings provide novel mechanistic insight and identify STAT3 as a direct molecular target of BBR in RA.

Serum creatine kinase (CK) is a routinely measured biomarker of muscle damage, yet the genetic factors underlying inter-individual variation in CK levels remain poorly defined. Here we present the largest multi-ancestry genome-wide association meta-analysis of serum CK to date, comprising 237,255 participants spanning Admixed American, African American, East Asian, European and Middle Eastern populations. We identify 107 independent loci at genome-wide significance (P<5x10 -8 ), 98 of which are previously unreported, with pronounced enrichment for genes expressed in skeletal and cardiac muscle and overlap with pathways related to muscle structure and function. Notably, eight loci map to genes implicated in Mendelian myopathies, underscoring a continuum from common regulatory variation to rare pathogenic mutations. Integrative quantitative trait locus (QTL)-based Mendelian randomization and colocalization implicate several genes in CK regulation, most prominently SMAD3 , KLF5 and STAT3 within the transforming growth factor beta signalling pathway. CK levels show positive genetic correlations with traits reflecting tissue damage and muscle mass, and negative correlations with C-reactive protein, indicating pleiotropic effects on muscle biology and enzyme clearance. Together, these findings delineate the genetic architecture of serum CK across diverse populations and provide insight into the genetic basis of muscle-damage risk and subclinical CK elevation.

This study aimed to investigate and analyze the clinical and immunological features of patients with anti-melanoma differentiation-associated gene-5 antibody-positive dermatomyositis (MDA5 + DM) complicated with clinical liver dysfunction. A cohort of 85 patients diagnosed with MDA5 + DM admitted into Peking University People’s Hospital from 2006 to 2023 were retrospectively enrolled in this study. Clinical characteristics and survival status were collected and analyzed. Clinical liver dysfunction occurred in 28

Myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are associated with distinctive dermatomyositis (DM) clinical phenotypes. The aim of this study is to explicate the clinical and immunological features of MSAs-negative DM patients. A total of 515 individuals diagnosed with DM was screened from 2013 to 2022 and 220 DM patients were enrolled in this retrospective cohort. Clinical and laboratory data of these patients were analyzed. MSAs-negative DM patients were categorized into two groups: MAAs-negative (MSAs (−)/MAAs (−)) group and MAAs-positive (MSAs (−)/MAAs (+)) group. The percentage of Raynaud’s phenomenon (P=0.026) was higher in the MSAs (−)/MAAs (+) DM patients than the MSAs-positive DM patients and MSAs (−)/MAAs (−) DM patients. The proportion of rapidly progressive interstitial lung disease (RP-ILD) in the MSAs-negative DM patients was lower than that in the MSAs-positive group. The MSAs (−)/MAAs (+) group had a higher proportion of organizing pneumonia and usual interstitial pneumonia (P=0.011), and elevated eosinophils in their bronchoalveolar lavage fluid (P=0.008). Counts of lymphocytes (P=0.001) and CD16+CD56+ natural killer (NK) cells (P=0.012) were higher in the MSAs-negative group. Additionally, the percentage of CD4+TNFα+ (P=0.040), CD4+IFNγ+ (P=0.037), and CD4+IL-2+ (P=0.018) cells among total CD4+ T cells were higher in the MSA-negative DM patients compared with the MSAs-positive DM patients. Besides, MSAs-negative patients demonstrated a more favorable prognosis than MSAs-positive patients. Multivariable regression analysis identified advanced onset age, higher level of carcinoembryonic antigen (CEA), and RP-ILD as risk factors for mortality in DM patients. Compared with MSAs-positive group, MSAs-negative DM patients suffered less from organ involvement compared with MSAs-positive group and tend to have better prognosis.

BACKGROUND:The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear.PURPOSE:The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo).STUDY-DESIGN/METHODS:Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP.RESULT:BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic.CONCLUSION:The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.