DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2019
·
IF 3.119
Liting Wu,Enxu Zhou,Along Gao,Linghe Kong,Siwei Wu,Xia Bian,Yuan Li,Bingxi Li,Shengli Fu,Zheng Guo,Jianmin Ye
B lymphocyte-induced maturation protein 1 (Blimp-1), a transcription factor containing zinc finger , is required and sufficient to trigger terminal differentiation of B cells in mammals. The Blimp-1 ( OnBlimp-1 ) from Nile tilapia ( Oreochromis niloticus ) was identified and characterized its expression pattern during B cell activation and maturation. The cDNA of OnBlimp-1 open reading frame is 2547 bp encoding a protein of 848 amino acids and the predicted molecular weight is 93.36 kDa. OnBlimp-1 contains a SET domain and five ZnF_C2H2 domains, which shares high homology with that of other species. OnBlimp-1 transcription was detected in all examined tissues with high expression in the spleen (SPL). Analysis of sorted lymphocyte populations , including IgM + and IgM − cells from peripheral blood (PBL), SPL and anterior kidney (AK), indicated that the OnBlimp-1 transcription was highly expressed in the IgM + B cells. Upon LPS stimulation, OnBlimp-1 expression was up-regulated in tissues of PBL, SPL and AK significantly. The expression of OnBlimp-1 , as well as the secreted IgM , was significantly up-regulated in the SPL and AK leukocytes stimulated with anti-OnIgM monoclonal antibody and LPS in vitro , respectively. Above results suggest that OnBlimp-1, a cytokine regulating the terminal differentiation of activated B cells to antibody-secreting cells, is likely to play important roles in B cell activation and maturation in Nile tilapia.
研究领域:
免疫学
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分子生物学
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鱼类生理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Hui Guo,Jiangtao Ma,Yanli Zhang,Yan Mao,Ziwei Hu,Ying Lin,Feng Yu,Wei Wang,Yaling Liu
An autoimmune condition known as systemic lupus erythematosus (SLE) is characterized by B cell hyperresponsiveness and persistent generation of pathogenic autoantibodies that cause damage to various organs and tissues. The treatments available today are either ineffective or have adverse effects. The dysregulation of B cell activation is crucial for the emergence of SLE. MiR-7 explicitly targeted PTEN mRNA in B cells. Treatment with antagomiR-7 reduced B cell hyperresponsiveness and prevented the onset of lupus. As a result, inhibiting miR-7 may be used therapeutically to treat SLE. We developed a SA (sialic acid)-poly (D, L-lactide-co-glycolide) (SA-PLGA) nano delivery system to deliver antagomiR-7 into splenic B cells since the stability and targeted delivery of miRNA remain significant challenges in vivo . Results show that SA-PLGA nanoparticles (SA-PLGA@antagomiR-7) loaded with antagomiR-7 display good biocompatibility and shield antagomiR-7 from degradation, extending the miRNA’s duration in circulation in vivo . Additionally, in MRL/Ipr lupus mice, SA-PLGA@antagomiR-7 is successfully delivered to the splenic B cells and preferentially enriched in the diseased spleen in MRL/Ipr lupus mice. The SA-PLGA@antagomiR-7 NPs therapy effectively decreases immunological abnormalities, normalizes splenic B cell subtypes, and suppresses B cell activation. The antagomiR-7 NPs exhibit excellent therapeutic efficiency and high biosafety collectively, which may result in a more effective treatment for SLE.
研究领域:
免疫学
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纳米技术
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Biomedicine
·
2025
·Vol. 6
·期 1
·1-18
·
IF 10.1
Yao Yu,Liu Yu-ying,Li Jian-feng,Chen Yun-shuo,Shi Lei,Shen Yang,Yang Li-li,Yang Qing
Acute myeloid leukemia (AML), the most common leukemia in adults, exhibits immune escape characteristics like solid tumors. The expression of indoleamine 2,3-dioxygenase 1 (IDO1), a well-recognized immune checkpoint, has been detected in AML blast cells and is associated with poor clinical outcome. Although an imbalance of B cell subpopulations exists in AML patients’ bone marrow microenvironment, the role of B cells and their interaction with IDO1 in AML have yet to be elucidated. Herein, with bioinformatic analysis, we found the close correlations between IDO1 expression and survival and B cell subpopulation proportions in AML patients. Further, our investigation into IDO1 expression and activity, B cell subpopulation proportions and immunosuppressive interleukin-10 (IL-10) level in AML cells and clinical samples revealed significant findings. Using a co-culture system of healthy human PBMCs and AML cell lines, we demonstrated that high IDO1 expression in AML cells could alter the proportions of total B, regulatory B and memory B cells, and increased the level of IL-10. Finally, with the IDO1 inhibitor RY103 designed by our laboratory, we found that IDO1 inhibition had good anti-leukemic effect and restored the abnormal proportions of B cell subpopulations in AML mice. Our study is the first to reveal the modulation of IDO1 on B cell subpopulations in AML, making a significant breakthrough in understanding the immune escape mechanisms of AML. Application of IDO1 inhibitor, such as RY103, targeting the imbalance of B cell subpopulations can lead to innovative treatments for AML.
研究领域:
肿瘤学
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免疫学
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血液学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Haixue Jia,Yuna Shang,Hongmei Cao,Yang Gao,Jinjian Liu,Lijun Yang,Cuihong Yang,Chunhua Ren,Zhongyan Wang,Jianfeng Liu
Compared with vaccines comprising inactivated or attenuated whole pathogens, the subunit vaccines based on protein antigens are safer and easier to manufacture. Yet subunit vaccines usually exhibit weak and nondurable immune responses, which is mainly due to their poor uptake by antigen-presenting cells. To address this issue, we develop a fluorinated aromatic peptide (F-AP), in which electronegativity of fluorine is to enhance its affinity with antigens and ability of transmembrane. In mice model, F-AP demonstrated over 4-fold and 501-fold higher antibody titers than AP and conventional aluminum adjuvant, respectively. Consistent with the antibody responses, F-AP greatly promoted the proliferation of T follicular helper cell and mature B cell. Intriguingly, conventional type 1 dendritic cells (cDC1) were also increased in lymph nodes with F-AP vaccination. And antigens localization experiments showed that F-AP help antigens escape from cell lysosomes, indicating that F-AP could potentially induce cellular immune responses through cDC1′s antigen cross-presentation function. Collectively, the data suggest that simple fluorine group modification on aromatic peptide, F-AP, could improve the immune response of subunit antigens. Thus, fluoridation strategy may provide a novel approach for nanomaterials enhancing the vaccination immune response of vaccines or immunotherapies.
研究领域:
免疫学
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疫苗学
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纳米生物技术
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肽化学
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产品关联
DOI
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Wenhao Zhong,Xinyu Zhang,Xiao Duan,Hengyu Liu,Yifen Fang,Moucheng Luo,Zhengwen Fang,Congxiu Miao,Dongjun Lin,Jun Wu
Gemcitabine , as a standard and classic strategy for B-cell lymphoma in the clinic, is limited by its poor pharmacodynamics . Although stimuli-responsive polymeric nanodelivery systems have been widely investigated in the past decade, issues such as complicated procedures, low loading capacity, and uncontrollable release kinetics still hinder their clinical translation. In view of the above considerations, we attempt to construct hyperbranched polyprodrug micelles with considerable drug loading via simple procedures and make use of the particularity of the tumor microenvironment to ensure that the micelles are “inactivated” in normal tissues and “activated” in the tumor microenvironment. Hence, in this work, a redox-responsive polymeric gemcitabine-prodrug (GEM-S-S-PEG) was one-pot synthesized via facile esterification and acylation . The self-assembled subsize (< 100 nm) GEM-S-S-PEG (GSP NPs) with considerable loading capacity (≈ 24.6%) exhibited on-demand and accurate control of gemcitabine release under a simulated tumor microenvironment and thus significantly induced the apoptosis of B-cell lymphoma in vitro . Moreover, in the A20 tumor xenograft murine model, GSP NPs efficiently decreased the expansion of tumor tissues with minimal systemic toxicity. In summary, these redox-responsive and self-assembling GSP NPs with a facile one-pot synthesis procedure may hold great potency in clinical translation for enhanced chemotherapy of B-cell lymphoma. Statement of significance A redox-responsive polymeric gemcitabine-prodrug (GEM-S-S-PEG) was one-pot synthesized via facile esterification and acylation. The self-assembled subsize (< 100 nm) GEM-S-S-PEG (GSP NPs) exhibited significant tumor therapeutic effects in vitro and in vivo . The polyprodrug GEM-S-S-PEG prepared in this study shows the great potential of redox-responsive nanodrugs for antitumor activity , which provides a reference value for the optimization of the design of functional polyprodrugs.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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DOI
PubMed
高影响因子
Anti-Cancer Agents in Medicinal Chemistry
·
2020
·Vol. 20
·期 13
·1571-1581
·
IF 2.049
Luo Yang,Fu Xiaoyi,Han Bin,Zhang Fafu,Yuan Lihong,Men Hongsheng,Zhang Shulin,Tian Sujuan,Dong Bin,Meng Minjie
Aims: The purpose of our study was to explore the combination effect of epirubicin and Bacillus Calmette Guerin (BCG) and its mechanism. Background: Bladder cancer is a threat to human health worldwide. Commonly used chemotherapy drugs and biotherapy have significant therapeutic
effects on bladder cancer, but the mechanism and combined effects are still unclear. Objective: To evaluate the anti-cancer effect of epirubicin combined with BCG on human bladder cancer cells, our studies were carried out. Methods: The viability of human bladder cancer cells with
epirubicin and/or BCG treatments was examined by Cell Counting Kit-8 (CCK-8) assay. Apoptosis and cell cycle phase were determined by flow cytometry analysis. Pre-apoptosis factors of caspase-3, p53, B-cell lymphoma 2 associated X protein (Bax) and anti-apoptosis factor of B-cell lymphoma
2 (Bcl-2) were detected by western blot. Results: The viability of human bladder cancer with epirubicin or BCG treatment was decreased and the viability with epirubicin combined with BCG treatment was decreased more, which were determined by CCK-8 assay. Both epirubicin and BCG increased
the apoptosis rate of human bladder cancer and arrested more cells into G0/G1 phase, which were tested by flow cytometry. The expression of caspase-3, p53 and Bax was increased and the expression of Bcl-2 was decreased with epirubicin treatment on human bladder cells, which were analyzed by
western blot. The expression of caspase-3 and p53 was increased with BCG treatment, which was examined by western blot. Conclusion: Epirubicin induced apoptosis in human bladder cancer cells by up-regulating the expression of proapoptotic factors (caspase-3, p53 and Bax) and down-regulating
the expression of anti-apoptotic factor (Bcl-2). BCG promoted apoptosis of human bladder cancer cells by up-regulating the expression of caspase-3 and p53. BCG plays a potential role at the time of the combination of epirubicin and BCG on bladder cancer cells in early stage. Both epirubicin
and BCG affected cell cycle distribution via arresting more bladder cancer cells at G0/G1 phase, which ultimately led bladder cancer proliferation in vitro and promoted apoptosis.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2021
·
IF 7.561
Wu Liting,Gao Along,Li Lan,Chen Jianlin,Li Jun,Ye Jianmin
Teleost fish anterior kidney (AK) is an important hematopoietic organ with multifarious immune cells, which have immune functions comparable to mammalian bone marrow. Myeloid and lymphoid cells locate in the AK, but the lack of useful specific gene markers and antibody-based reagents for the cell subsets makes the identification of the different cell types difficult. Single-cell transcriptome sequencing enables single-cell capture and individual library construction, making the study on the immune cell heterogeneity of teleost fish AK possible. In this study, we examined the transcriptional patterns of 11,388 AK leukocytes using 10× Genomics single-cell RNA sequencing (scRNA-seq). A total of 22 clusters corresponding to five distinct immune cell subsets were identified, which included B cells, T cells, granulocytes, macrophages, and dendritic cells (DCs). However, the subsets of myeloid cells (granulocytes, macrophages, and DCs) were not identified in more detail according to the known specific markers, even though significant differences existed among the clusters. Thereafter, we highlighted the B-cell subsets and identified them as pro/pre B cells, immature/mature B cells, activated B/plasmablasts, or plasma cells based on the different expressions of the transcription factors (TFs) and cytokines. Clustering of the differentially modulated genes by pseudo-temporal trajectory analysis of the B-cell subsets showed the distinct kinetics of the responses of TFs to cell conversion. Moreover, we classified the T cells and discovered that CD3+CD4−CD8−, CD3+CD4+CD8+, CD4+CD8−, and CD4−CD8+ T cells existed in AK, but neither CD4+CD8− nor CD4−CD8+ T cells can be further classified into subsets based on the known TFs and cytokines. Pseudotemporal analysis demonstrated that CD4+CD8− and CD4−CD8+ T cells belonged to different states with various TFs that might control their differentiation. The data obtained above provide a valuable and detailed resource for uncovering the leukocyte subsets in Nile tilapia AK, as well as more potential markers for identifying the myeloid and lymphoid cell types.
研究领域:
免疫学
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鱼类生物学
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分子生物学
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DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Zhihua Wang,Mingda Han,Yiqiao Wang,Ning Wang,Yilin Yang,Bingru Shao,Qiannan Miao,Zhan Shi,Fei Yan,Shouhua Feng
B-cell lymphoma (BCL) is a hematological malignancy with high heterogeneity and represents an aggressive proliferation of mature B-cells. Despite the initial success of traditional treatments for BCL in clinical trials, a majority of patients eventually develop resistance to therapy and have poor clinical outcomes. Epigenetic dysregulation is a major contributor to the pathogenesis of BCL, and therapies targeting epigenetic pathways is a promising alternative strategy for treating BCL. Herein, we developed a metal–organic framework (MOF)-based nano-sonosensitizer for ultrasound-driven cascade immunotherapy against BCL. The nano-sonosensitizer was synthesized by encapsulating copper complex of the m6A-mRNA demethylase inhibitor into UiO-66-NH2, which possesses a Z-scheme heterostructure and allows efficient electron–hole pair separation for generating reactive oxygen species (ROS) under ultrasound activation. These CuR@UiO66 sonosensitizers were functionalized with mPEG-PO3 and anti-CD19 antibody, and the resulting CRUPPA19 particles could specifically accumulate in the BCL tissue and also target lymphoma cells that infiltrated into the bone marrow. Once internalized, CRUPPA19 could induce intracellular ROS production and apoptosis under ultrasound irradiation. Subsequently, ultrasonic stimulation triggered autophagy-mediated release of Cu and Rhein from CRUPPA19, thereby increasing protein lipoylation and global mRNA methylation, which led to cuproptosis and the transcriptional repression PDL1, respectively. These cascades synergistically induced immunogenic cell death in the tumors and promoted activation of CD8+ T cells, eventually leading to an antilymphoma immune response. CRUPPA19-mediated sono-immunotherapy not only eliminated the primary and metastatic lymphomas but also cleared lymphoma cells from the bone marrow. This study provided an insight into a MOF-based nanoepigenetic therapy platform with ultrasound-triggered cascade amplification for enhanced antihematological tumor immunity.
研究领域:
肿瘤学
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生物医学工程
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免疫学
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产品关联
DOI
PubMed
高影响因子
LEUKEMIA RESEARCH
·
2021
·
IF 3.156
Mi Mi,Zijian Liu,Xin Zheng,Qiuyue Wen,Fang Zhu,Juan Li,Ishanee Devi Mungur,Liling Zhang
Background The varied clinical outcomes of patients with Diffuse Large B Cell Lymphoma (DLBCL) are attributed to the different genetic and phenotypic subtypes. The purpose of this study was to determine whether metabolic alterations were related to cell-of-origin subtypes of DLBCL and find some metabolites which are associated with the clinical outcomes. Methods Pre-treatment serum samples from eighty (80) newly diagnosed DLBCL patients, including twenty-eight (28) patients with Germinal Center B cell-like (GCB) subtypes and fifty-two (52) patients with non-GCB subtypes, were tested by the Gas Chromatography-Mass Spectrometry (GC–MS) technique. Univariate and multivariate analysis methods, principal component analysis (PCA), and partial least square discriminant analysis (PLS-DA) were conducted to examine the potential differential metabolites. Overall survival (OS) was calculated. Results Overall, 65 out of 1472 entities were identified for subsequent analysis. Unfortunately, the initial PLS-DA analysis failed to discriminate GCB from non-GCB samples. Intriguingly, further PLS-DA analysis identified two subgroups of DLBCL (named as group A and group B) and the metabolic subgroups were significantly associated with overall survival. Valine, hexadecenoic acid, and pyroglutamic acid were identified and verified as the most important altered metabolites and could be candidate biomarkers for the prognosis of DLBCL. Conclusions Our results demonstrated that metabolic alterations in serum could be helpful to predict different clinical outcomes of DLBCL patients. Further studies are warranted to understand whether the altered metabolites might serve as prognostic factors for DLBCL.
研究领域:
肿瘤学
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代谢组学
·
医学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Zuchen Song,Lina Jiao,Deyun Wang,Yawei Qiu,Jinfeng Miao,Tianyu Zhu,Ruihong Yu,Zheng Wang,Yantong Zhou,Ting Cai,Shun Zhang,Huina Liu,Haifeng Sun,Yuechao Sun,Zhenguang Liu
Vaccines are an effective intervention for preventing infectious diseases. Currently many vaccine strategies are designed to improve vaccine efficacy by controlling antigen release, typically involving various approaches at the injection site. Yet, strategies for intracellular slow-release of antigens in vaccines are still unexplored. Our study showed that controlling the degradation of antigens in dendritic cells and slowing their transport from early endosomes to lysosomes markedly enhances both antigen-specific T-cell immune responses and germinal center B cell responses. This leads to the establishment of sustained humoral and cellular immunity in vivo imaging and flow cytometry indicated this method not only prolongs antigen retention at the injection site but also enhances antigen concentration in lymph nodes, surpassing traditional Aluminium (Alum) adjuvants. Additionally, we demonstrated that the slow antigen degradation induces stronger follicular helper T cell responses and increases proportions of long-lived plasma cells and memory B cells. Overall, these findings propose that controlling the speed of antigens transport in dendritic cells can significantly boost vaccine efficacy, offering an innovative avenue for developing highly immunogenic next-generation vaccines.
研究领域:
免疫学
·
疫苗学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Targeted Oncology
·
2020
·Vol. 15
·期 3
·365-375
·
IF 4.036
Ding Shengnan,Mao Xia,Cao Yang,Wang Na,Xu Hao,Zhou Jianfeng
Background Although chimeric antigen receptor (CAR) T-cell therapy targeting antigens expressed in refractory and relapsed non-Hodgkin B-cell lymphoma, such as CD19 and CD22, has achieved encouraging clinical effects, some patients fail to attain remission, or relapse after CAR T-cell therapy, which has been ascribed to the loss of the target antigens. Objective To evaluate CD79b as an alternative target for CAR T-cell B-cell lymphoma therapy. Patient and methods The expression of CD79b in different B-cell lymphomas was determined. Anti-CD79b CAR T-cells expressing one of two different CARs were generated, and a series of in vitro and in vivo experiments were conducted to assess the CAR T-cell function. Results We found that CD79b was extensively expressed on the tumor cells of patients with various types of lymphoma regardless of stage, subtype, and cytogenetic and molecular features. Anti-CD79b CAR T-cells were highly specific and effective for the treatment of B-cell lymphomas. Conclusions Our data indicate that CD79b could be used as a target for CAR T-cell therapy of B-cell lymphomas, and further clinical development is warranted.
研究领域:
肿瘤学
·
免疫学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
AQUACULTURE
·
2020
·
IF 3.225
Kailiang Han,Liting Wu,Liangliang Mu,Hairong Wu,Xia Bian,Zheng Guo,Xiaoxue Yin,Jianmin Ye
B cell linker protein (BLNK), an adapter of SLP-76 family, plays an extremely important role in B cell receptor (BCR) signaling pathway that regulates proliferation, differentiation, and apoptosis of B cell. BLNK participates in the signal transduction of BCR activation through its typical structure and interaction network with SYK, BTK etc. In this study, Nile tilapia BLNK (OnBLNK) open reading frame is 1470 bp in length for 489 amino acids. OnBLNK composes of a SAM domain at the N-terminal, a central proline-rich region and a highly conserved SH2 domain containing four conserved YXXP tyrosine phosphorylation sites at the C-terminal. Alignment of BLNK sequence and phylogenetic analysis indicated that OnBLNK was highly homologous to that of other teleost fish and mammals. Tissue distribution analysis revealed that OnBLNK showed a wide distribution in all examined tissues and with the highest expression in head kidney . After challenge with Streptococcus agalactiae ( S. agalactiae ) in vivo , the OnBLNK expression was significantly up-regulated in spleen and head kidney. In addition, the significant up-regulation of OnBLNK mRNA expression was also observed in head kidney leukocytes (HKLs) stimulated with S. agalactiae and lipopolysaccharide (LPS) in vitro . Further, it was also demonstrated that expression of OnBLNK mRNA was obviously up-regulated when HKLs were stimulated by mouse anti-tilapia IgM monoclonal antibody in vitro , and declined to normal after treatment with LYN, SYK or BTK inhibitor, respectively. Overall, the results suggest that OnBLNK might take part in host defense during bacterial infection, and get involved in the BCR signaling pathway. This study might aid to better understand the regulatory mechanism of BCR signaling pathway in teleost fish.
研究领域:
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
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