Nuclear receptor estrogen-related receptor gamma suppresses colorectal cancer aggressiveness by regulating Wnt/ß-catenin signaling.

Colorectal cancer (CRC) is the predominant cause of cancer-related death worldwide, because of the lack of effective therapeutic targets. Estrogen-related receptor gamma (ESRRG), which belongs to the family of nuclear receptors, functions as an important element regulating gene transcription. In our report, we identified ESRRG as a potential tumor suppressor. The decreased level of ESRRG was initially observed in CRC and was highly associated with a poor prognosis. ESRRG overexpression abrogated cell growth and metastasis in vitro and in vivo. Mechanistically, ESRRG repressed the epithelial-to-mesenchymal transition process and antagonized Wnt signaling by regulating ß-catenin degradation. In addition, significant ESRRG hypermethylation was found in CRC and inversely correlated with its expression. Consistently, the expression of ESRRG was induced after treatment with DNA demethylating agent 5-aza-2'-deoxycytidine. Taken together, these findings define a tumor-suppressive role of ESRRG in CRC, providing a potential novel therapeutic approach for this cancer.

Correction to: Exosomes derived from atorvastatin-modified bone marrow dendritic cells ameliorate experimental autoimmune myasthenia gravis by up-regulated levels of IDO/Treg and partly dependent on FasL/Fas pathway.

After the publication of the original article [1], it came to the authors' attention that there was an error in the originally published version of Fig. 5b. The image of CD4+CD25+ T cells of the statin-Dex group was unintentionally replaced with the image of CD4+CD25+ T cells from the control group. The correct version of Fig. 5b is published in this Erratum.

Enhanced glycolysis contributes to the pathogenesis of experimental autoimmune neuritis.

BACKGROUND: With the recognition of the key roles of cellular metabolism in immunity, targeting metabolic pathway becomes a new strategy for autoimmune disease treatment. Guillain-Barré syndrome (GBS) is an acute immune-mediated inflammatory demyelinating disease of the peripheral nervous system, characterized by inflammatory cell infiltration. These inflammatory cells, including activated macrophages, Th1 cells, and Th17 cells, generally undergo metabolic reprogramming and rely mainly on glycolysis to exert functions. This study aimed to explore whether enhanced glycolysis contributed to the pathogenesis of experimental autoimmune neuritis (EAN), a classic model of GBS. METHODS: Preventive and therapeutic treatments with glycolysis inhibitor, 2-deoxy-D-glucose (2-DG), were applied to EAN rats. The effects of treatments were determined by clinical scoring, weighting, and tissue examination. Flow cytometry and ELISA were used to evaluate T cell differentiation, autoantibody level, and macrophage functions in vivo and in vitro. RESULTS: Glycolysis inhibition with 2-DG not only inhibited the initiation, but also prevented the progression of EAN, evidenced by the improved clinical scores, weight loss, inflammatory cell infiltration, and demyelination of sciatic nerves. 2-DG inhibited the differentiation of Th1, Th17, and Tfh cells but enhanced Treg cell development, accompanied with reduced autoantibody secretion. Further experiments in vitro proved glycolysis inhibition decreased the nitric oxide production and phagocytosis of macrophages and suppressed the maturation of dendritic cells (DC). CONCLUSION: The effects of glycolysis inhibition on both innate and adaptive immune responses and the alleviation of animal clinical symptoms indicated that enhanced glycolysis contributed to the pathogenesis of EAN. Glycolysis inhibition may be a new therapy for GBS.

ROCK inhibitor abolishes the antibody response in experimental autoimmune myasthenia gravis.

The Rho/Rho kinase (ROCK) pathway serves as molecular switches in many biological processes including the immune response. ROCK inhibitors lead to amelioration of some autoimmune diseases. The present study was designed to define whether a selective ROCK inhibitor, fasudil, was effective in experimental autoimmune myasthenia gravis (EAMG) and investigate the underlying mechanisms. Here we found fasudil effectively attenuated the development of ongoing EAMG. Fasudil abolished the antibody production and function by decreasing follicular helper T cells and CD19(+) B cells, especially germinal center B cells. Moreover, fasudil reduced the expression of CD80 on lymph node mononuclear cells. These findings suggest the inhibition of ROCK might be a potential therapeutic strategy for antibody-mediated autoimmune diseases.

Exosomes derived from atorvastatin-modified bone marrow dendritic cells ameliorate experimental autoimmune myasthenia gravis by up-regulated levels of IDO/Treg and partly dependent on FasL/Fas pathway.

BACKGROUND: Previously, we have demonstrated that spleen-derived dendritic cells (DCs) modified with atorvastatin suppressed immune responses of experimental autoimmune myasthenia gravis (EAMG). However, the effects of exosomes derived from atorvastatin-modified bone marrow DCs (BMDCs) (statin-Dex) on EAMG are still unknown. METHODS: Immunophenotypical characterization of exosomes from atorvastatin- and dimethylsulfoxide (DMSO)-modified BMDCs was performed by electron microscopy, flow cytometry, and western blotting. In order to investigate whether statin-DCs-derived exosomes (Dex) could induce immune tolerance in EAMG, we administrated statin-Dex, control-Dex, or phosphate-buffered saline (PBS) into EAMG rats via tail vein injection. The tracking of injected Dex and the effect of statin-Dex injection on endogenous DCs were performed by immunofluorescence and flow cytometry, respectively. The number of Foxp3(+) cells in thymuses was examined using immunocytochemistry. Treg cells, cytokine secretion, lymphocyte proliferation, cell viability and apoptosis, and the levels of autoantibody were also carried out to evaluate the effect of statin-Dex on EAMG rats. To further investigate the involvement of FasL/Fas in statin-Dex-induced apoptosis, the underlying mechanisms were studied by FasL neutralization assays. RESULTS: Our data showed that the systemic injection of statin-Dex suppressed the clinical symptoms of EAMG rats. These statin-Dex had immune regulation functions in immune organs, such as the spleen, thymus, and popliteal and inguinal lymph nodes. Furthermore, statin-Dex exerted their immunomodulatory effects in vivo by decreasing the expression of CD80, CD86, and MHC class II on endogenous DCs. Importantly, the therapeutic effects of statin-Dex on EAMG rats were associated with up-regulated levels of indoleamine 2,3-dioxygenase (IDO)/Treg and partly dependent on FasL/Fas pathway, which finally resulted in decreased synthesis of anti-R97-116 IgG, IgG2a, and IgG2b antibodies. CONCLUSIONS: Our data suggest that atorvastatin-induced immature BMDCs are able to secrete tolerogenic Dex, which are involved in the suppression of immune responses in EAMG rats. Importantly, our study provides a novel cell-free approach for the treatment of autoimmune diseases.

Statin-modified dendritic cells regulate humoral immunity in experimental autoimmune myasthenia gravis.

We previously demonstrated that atorvastatin induced immature dendritic cells (DCs) derived from spleen in vitro. Administration of these tolerogenic DCs led to amelioration of experimental autoimmune myasthenia gravis (EAMG). The protective effect was mainly mediated by inhibited cellular immune response, including up-regulated regulatory T cells and shifted Th1/Th17 to Th2 cytokines. The present study employed atorvastatin-modified bone marrow-derived DCs (AT-BMDCs) to explore the effect of tolerogenic DCs on humoral immune response of EAMG and further elucidate the underlying mechanisms. Our data showed that AT-BMDCs reduced the quantity and the relative affinity of pathogenic antibodies, suppressed germinal center response, decreased follicular helper T cells and IL-21, and increased regulatory B cells. These results suggest that AT-BMDCs ameliorate EAMG by regulating humoral immune response, thus providing new insights into therapeutic approaches of myasthenia gravis and other autoimmune diseases.

Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in Candida albicans.

Fungal infections, especially infections caused by Candida albicans, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in C. albicans are needed. Knowledge of growth and virulence in fungal cells is essential not only to understand their pathogenic mechanisms but also to identify potential antifungal targets. This article reviews the current knowledge of the mechanisms of growth and virulence in C. albicans and examines potential targets for the development of new antifungal drugs.

Caspase-1 inhibitor ameliorates experimental autoimmune myasthenia gravis by innate dendric cell IL-1-IL-17 pathway.

BACKGROUND: IL-1ß has been shown to play a pivotal role in autoimmunity. Cysteinyl aspartate-specific proteinase-1 (caspase-1) inhibitor may be an important drug target for autoimmune diseases. However, the effects of caspase-1 inhibitor on myasthenia gravis (MG) remain undefined. METHODS: To investigate the effects of caspase-1 inhibitor on experimental autoimmune myasthenia gravis (EAMG), an animal model of MG, caspase-1 inhibitor was administered to Lewis rats immunized with region 97-116 of the rat AChR α subunit (R97-116 peptide) in complete Freund's adjuvant. The immunophenotypical characterization by flow cytometry and the levels of autoantibody by ELISA were carried out to evaluate the neuroprotective effect of caspase-1 inhibitor. RESULTS: We found that caspase-1 inhibitor improved EAMG clinical symptom, which was associated with decreased IL-17 production by CD4+ T cells and γδ T cells, lower affinity of anti-R97-116 peptide IgG. Caspase-1 inhibitor decreased expression of CD80, CD86, and MHC class II on DCs, as well as intracellular IL-1ß production from DCs. In addition, caspase-1 inhibitor treatment inhibited R97-116 peptide-specific cell proliferation and decreased follicular helper T cells relating to EAMG development. CONCLUSIONS: Our results suggest that caspase-1 inhibitor ameliorates experimental autoimmune myasthenia gravis by innate DC IL-1-IL-17 pathway and provides new evidence that caspase-1 is an important drug target in the treatment of MG and other autoimmune diseases.

Atorvastatin-modified dendritic cells in vitro ameliorate experimental autoimmune myasthenia gravis by up-regulated Treg cells and shifted Th1/Th17 to Th2 cytokines.

Conventional therapies for autoimmune diseases produce nonspecific immune suppression, which are usually continued lifelong to maintain disease control, and associated with a variety of adverse effects. In this study, we found that spleen-derived dendritic cells (DCs) from the ongoing experimental autoimmune myasthenia gravis (EAMG) rats can be induced into tolerogenic DCs by atorvastatin in vitro. Administration of these tolerogenic DCs to EAMG rats on days 5 and 13 post immunization (p.i.) resulted in improved clinical symptoms, which were associated with increased numbers of CD4(+)CD25(+) T regulatory (Treg) cells and Foxp3 expression, decreased lymphocyte proliferation among lymph node mononuclear cells (MNC), shifted cytokine profile from Th1/Th17 to Th2 type cytokines, decreased level of anti-R97-116 peptide (region 97-116 of the rat acetylcholine receptor α subunit) IgG antibody in serum. These tolerogenic DCs can migrate to spleen, thymus, popliteal and inguinal lymph nodes after they were injected into the EAMG rats intraperitoneally. Furthermore, these tolerogenic DCs played their immunomodulatory effects in vivo mainly by decreased expression of CD86 and MHC class II on endogenous DCs. All these data provided us a new strategy to treat EAMG and even human myasthenia gravis (MG).

[Contamination of typical human enteric viruses in economic shellfish along the Chinese coast].

OBJECTIVE: The objective of this study is to understand the contamination of human enteric viruses in economic shellfish along the Chinese coast, an important issue of ensuring the seafood safety. METHODS: We established the specific, sensitive and high-throughput gene chip technology, to investigate the contamination of economic shellfish by enteric viruses across a large geographical region of China. RESULTS: The percentage of positive samples for each virus was as follows: Hepatitis A Virus 4.3%, norovirus 14.8%, rotavirus 6.2%, astrovirus 5.6%, and adenovirus 9.9%. In these five viruses, norovirus was contaminated in the first place. The results detected by gene chip were highly consistent with that of polymerase chain reaction (PCR). The economic shellfishes in shellfish-growing areas along the coastal cities were all contaminated with enteric viruses at different levels. However, there was no significant correlation between any two cities. In the selected 6 economic shellfishes, oyster had the highest positive rate of enteric viruses, followed by blood clam. CONCLUSION: The contamination of shellfish with human enteric viruses was common across the main coastal cities of China, indicating a potential public health threat from seafood.

Correlation of N-myc downstream-regulated gene 1 subcellular localization and lymph node metastases of colorectal neoplasms.

In colorectal neoplasms, N-myc downstream-regulated gene 1 (NDRG1) is a primarily cytoplasmic protein, but it is also expressed on the cell membrane and in the nucleus. NDRG1 is involved in various stages of tumor development in colorectal cancer, and it is possible that the different subcellular localizations may determine the function of NDRG1 protein. Here, we attempt to clarify the characteristics of NDRG1 protein subcellular localization during the progression of colorectal cancer. We examined NDRG1 expression in 49 colorectal cancer patients in cancerous, non-cancerous, and corresponding lymph node tissues. Cytoplasmic and membrane NDRG1 expression was higher in the lymph nodes with metastases than in those without metastases (P<0.01). Nuclear NDRG1 expression in colorectal neoplasms was significantly higher than in the normal colorectal mucosa, and yet the normal colorectal mucosa showed no nuclear expression. Furthermore, our results showed higher cytoplasmic NDRG1 expression was better for differentiation, and higher membrane NDRG1 expression resulted in a greater possibility of lymph node metastasis. These data indicate that a certain relationship between the cytoplasmic and membrane expression of NDRG1 in lymph nodes exists with lymph node metastasis. NDRG1 expression may translocate from the membrane of the colorectal cancer cells to the nucleus, where it is involved in lymph node metastasis. Combination analysis of NDRG1 subcellular expression and clinical variables will help predict the incidence of lymph node metastasis.

Dysfunction of peripheral regulatory T cells predicts lung injury after cardiopulmonary bypass.

Lung injury caused by cardiopulmonary bypass (CPB) increases the mortality after cardiac surgery. Previous studies have shown that regulatory T cells (Tregs) play a protective role during CPB, but the correlation between Tregs and CPB-induced lung injury remains unclear. Here, we conducted a prospective study about Treg cells in patient receiving CPB. Treg cells were collected from patients before the CPB operation (pre-CPB Tregs), and the effect of pre-CPB Tregs on the occurrence of CPB-induced lung injury was evaluated. Data showed that the baseline level of Treg cells in peripheral blood were lower in patients who developed lung injury after CPB, compared to those who did not develop lung injury after CPB. Function analyses revealed that pre-CPB Tregs from CPB-induced lung injury patients presented decreased ability in suppressing the proliferation and IFN-γ production of CD4 and CD8 T cell. Also, pre-surgery levels of TGF- ß and IL-10 were markedly lower in lung injury patients than in non-lung injury patients. In addition, PD-1 and Tim-3 expression on pre-CPB Tregs were significantly lower in CPB-induced lung injury patients than the CPB patients without lung injury. Above all, we found impaired peripheral Treg responses in CPB-induced lung injury patients, indicating a potential role of Treg cells in the early diagnosis of CPB-induced lung injury.

Identification and functional analysis of lncRNAs and mRNAs between tumorigenesis and metastasis in CRC.

The role of long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) tumorigenesis and metastasis remains poorly characterized. The aim of this study was to identify novel lncRNAs and their functions in CRC progression. Through microarray analysis of paired normal colorectal mucosa (NM), primary tumor (PT), and metastatic lymph node (MLN) tissues, lncRNA and mRNA expression patterns were identified. Further bioinformatic analyses were performed to compare the biological functions of lncRNAs between tumorigenesis and metastasis of CRC, which was further verified by TCGA-COAD and GSE82236. The expression of lncRNA MIR29B2CHG93 in paired CRC tissues was detected in a cohort of CRC patients. The effects of lncRNA MIR29B2CHG93 on proliferation, migration, and invasion were determined by in vitro experiments. We found that tumorigenesis-associated lncRNAs predominantly participated in the regulation of the EMT/P53/PI3K-Akt/KRAS signaling pathway as well as the processes related to cell cycle and cell mitosis, while metastasis-associated lncRNAs mainly regulated blood vessel morphogenesis and immune-related biological processes. Compared to the TCGA and GSE datasets, seven tumorigenesis-associated lncRNAs and eight metastasis-associated lncRNAs were identified. LncRNA MIR29B2CHG93 knockdown remarkably suppressed tumor growth and metastasis in vitro, which acted as a tumor promoter in CRC. The lncRNA MIR29B2CHG93 was significantly upregulated in CRC tissues and was indicator of unfavorable clinical outcome in CRC. These results revealed novel lncRNAs that provide new insights for an in-depth understanding of CRC progression. In particular, this study identified a novel lncRNA MIR29B2CHG93 in CRC progression, which might be a potential biomarker for diagnosis, prognosis and metastasis-prediction in CRC.

FLRT2 functions as Tumor Suppressor gene inactivated by promoter methylation in Colorectal Cancer.

Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epigenetic alterations, especially DNA methylation, contribute to the initiation and progression of CRC. To identify novel methylated tumor suppressors in CRC, MethylRAD-Seq screening was performed. As the result, FLRT2 was found to be preferentially methylated. In the present study, we aimed to elucidate the epigenetic regulations and biological functions of FLRT2 in CRC. Significant FLRT2 hypermethylation was initially confirmed in CRC samples and cell lines. Meanwhile, downregulated expression of FLRT2 was observed in CRC, which is probably attributed to promoter methylation of FLRT2. Consistently, the expression of FLRT2 was restored after treatment with DNA demethylating agent 5-AZA. FLRT2 overexpression resulted in impaired cell viability and colony formation. Additionally, FLRT2 overexpression led to a reduction in cell migration and cell invasion. Furthermore, we also observed that FLRT2 induced cell cycle arrest. Mechanistically, these effects were associated with the downregulation of phosphor-AKT, phosphor-ERK, CDK2, Cyclin A, and MMP2, and upregulation of P21. Taken together, these results define a tumor-suppressor role of FLRT2 with epigenetic silencing in the pathogenesis of CRC. Moreover, FLRT2 promoter methylation may be a useful epigenetic biomarker for the prevention and treatment of CRC.

Toll-like receptor 9 antagonist suppresses humoral immunity in experimental autoimmune myasthenia gravis.

Recent studies have demonstrated the important role of toll-like receptor 9 (TLR9) signalling in autoimmune diseases, but its role in myasthenia gravis (MG) has not been fully established. We show herein that blocking TLR9 signalling via the suppressive oligodeoxynucleotide (ODN) H154 alleviated the symptoms of experimental autoimmune myasthenia gravis (EAMG). With the downregulation of dendritic cells (DCs), TLR9 interruption reduced follicular helper T cells (Tfh) and germinal centre (GC) B cells, leading to decreased antibody production. In addition, TLR9+ B cells as well as total B cells in the spleen were inhibited by H154. These findings highlight the critical role of TLR9 in EAMG and suggest that the inhibition of the TLR9 pathway might be a potential pharmacological strategy for the treatment of myasthenia gravis.

Statins reduce the expressions of Tim-3 on NK cells and NKT cells in atherosclerosis.

3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have an immuno-regulatory effect in addition to lowing-lipids. Accumulated evidence showed that the expressions of T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) on natural killer (NK) cells increased in atherosclerotic patients and animal models. In this study, 14 patients treated with rosuvastatin and 12 patients with atorvastatin for more than 3 months were included and 20 patients without statins treatment as control. Both statins treatment reduced the expressions of Tim-3 on NK cells and their subtypes, natural killer T (NKT) cells and CD3+ T cells, and increased the proportions of NKT cells among peripheral blood mononuclear cells, accompanied by the decreased levels of total cholesterol, low density lipoprotein, and increased ratios of high density lipoprotein to cholesterol. These may contribute to the functions of statins in the treatment of atherosclerosis.

Secretory Clusterin Mediates Oxaliplatin Resistance via the Gadd45a/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma.

Purpose: Systemic therapy has often been used for patients with advanced hepatocellular carcinoma (HCC). However, due to drug resistance, the use of cytotoxic chemotherapy in the treatment of patients with advanced HCC has typically demonstrated low response rates. Secretory clusterin (sCLU) is expressed in aggressive late-stage tumors and associated with resistance to chemotherapy, including that in HCC cases. The present research aimed to investigate the biological role of sCLU in HCC. Methods: sCLU expression in HCC and normal tissues was examined using immunohistochemical staining, followed by analysis of the correlation between sCLU expression and clinical indicators. In addition, the role and internal mechanism of sCLU in cell proliferation and apoptosis were investigated in HCC cells. Results: sCLU expression was significantly upregulated in HCC tissues; and was associated with histological grade and poor overall survival. The levels of sCLU were significantly increased in Bel7402, SMMC7721 and resistant HCC cells (Bel7404-OR). Inhibiting the activity of sCLU enhanced the chemosensitivity of Bel7402 and SMMC7721 cells. Downregulation of sCLU could increase the expression of Gadd45a in HCC cells. Overexpression of sCLU contributed to drug resistance in Bel7402, SMMC7721 and Bel7404-OR cells; whereas, overexpression of Gadd45a alone overcame drug resistance in the cells above. No significant expression changes of sCLU and Gadd45a were observed in HCC cells after the interference of a selective inhibitor of the PI3K/Akt signaling pathway. However, regulation of the expression of Gadd45a could influence the phosphorylation level of Akt; and further regulate the expression of Bcl-2 and Bax proteins involved in the mitochondrial apoptosis pathways. Conclusions: The results demonstrate that sCLU/Gadd45a/PI3K/Akt signaling represents a novel pathway that could regulate drug resistance in a one-way manner in HCC cells.

N-myc downstream-regulated gene 1 inhibits the proliferation and invasion of hepatocellular carcinoma cells via the regulation of integrin ß3.

N-myc downstream-regulated gene 1 (NDRG1) is a multifunctional protein associated with carcinogenesis and tumor progression. The function of NDRG1 in hepatocellular carcinoma (HCC) cells remains controversial. The present study investigated the role of NDRG1 in HCC as well as its molecular mechanism using a range of techniques, including western blot analysis, cellular proliferation test, wound healing assay and Transwell assay. In HCC, the levels of NDRG1 expression were highest in the cytoplasm, followed by the membrane, and were lowest in the nucleus. NDRG1 was revealed to inhibit the proliferation and invasion of BEL7402 cells, which facilitated the hypothesis that NDRG1 expression levels may be lower in cell line with a high metastatic potential compared with those in cell lines with a low metastatic potential. However, the present study identified that NDRG1 expression was higher in detached BEL7402 cells and MHCC-97H cells compared with that in attached BEL7402 cells and MHCC-97L cells. Thus, this finding was contrary to what was expected, suggesting that NDRG1 overexpression in the HCC with a high metastatic potential may be the compensatory mechanism. The human HCC BEL7402 cell line demonstrated a significant increase in the capability of motility, invasion and cellular proliferation following NDRG1-short hairpin RNA transfection. Integrin ß3 (ITGB3) protein expression was increased in NDRG1-downregulated BEL7402 cells and SMMC7721 cells compared with that in the control cells. The present study suggested that NDRG1 may be a potential anti-tumor target for the treatment of patients with HCC. A potential mechanism for these roles of NDRG1 is by regulating ITGB3 expression; however, this requires additional investigation.

ONX-0914, a selective inhibitor of immunoproteasome, ameliorates experimental autoimmune myasthenia gravis by modulating humoral response.

Accumulating evidence shows that the immunoproteasome participates in the immune response, beyond its initial role in the protein degradation. Here, we tested the effects of the selective immunoproteasome inhibitor, ONX-0914, on experimental autoimmune myasthenia gravis (EAMG). We found that ONX-0914 ameliorated the severity of ongoing EAMG by reducing the autoantibody affinity, accompanied with decreased Tfh cells and antigen presenting cells. Also it reduced the percentage of Th17 cells and inhibited the secretion of IL-17. Our data indicated ONX-0914 may bring benefit for MG therapy.

Caspase-1 inhibitor regulates humoral responses in experimental autoimmune myasthenia gravis via IL-6- dependent inhibiton of STAT3.

We have previously demonstrated that Cysteinyl aspartate-specific proteinase-1 (caspase-1) inhibitor ameliorates experimental autoimmune myasthenia gravis (EAMG) by inhibited cellular immune response, via suppressing DC IL-1 ß, CD4+ T and γdT cells IL-17 pathways. In this study, we investigated the effect of caspase-1 inhibitor on humoral immune response of EAMG and further explore the underlying mechanisms. An animal model of MG was induced by region 97-116 of the rat AChR α subunit (R97-116 peptide) in Lewis rats. Rats were treated with caspase-1 inhibitor Ac-YVAD-cmk intraperitoneally (i.p.) every second day from day 13 after the first immunization. Flow cytometry, western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the neuroprotective effect of caspase-1 inhibitor on humoral immune response of EAMG. The results showed that caspase-1 inhibitor reduced the relative affinity of anti-R97-116 IgG, suppressed germinal center response, decreased follicular helper T cells, and increased follicular regulatory T cells and regulatory B cells. In addition, we found that caspase-1 inhibitor inhibited humoral immunity response in EAMG rats via suppressing IL-6-STAT3-Bcl-6 pathways. These results suggest that caspase-1 inhibitor ameliorates EAMG by regulating humoral immune response, thus providing new insights into the development of myasthenia gravis and other autoimmune diseases therapies.