CELLULAR SIGNALLING
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2025
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IF 3.7
Jie Liu,Mei-qi He,Gao-peng Guan,Xin-xing Wan,Ping Jin
Type 1 diabetes (T1D) is an autoimmune disease characterized by hyperglycemia caused by the destruction of insulin-producing β cells. Viral infection is an important environmental factor which is associated with the islet autoimmunity in genetically susceptible individuals. Loss of β-cells and triggering of insulitis following viral infection could result from several non-exclusive mechanisms. Despite a significant increase in ISG15 levels following viral infection, the specific role of ISG15 in the impairment of insulin-producing β-cells is unclear. To address this issue at the clinical level, we conducted this experimental work, and found elevated levels of ISG15 in the peripheral blood of T1D patients, suggesting a potential link between ISG15 and T1D. In the T1D animal model, we discovered that both ISG15 levels and cellular apoptosis were increased in pancreatic islet tissue. To investigate at the cellular level, we cultured MIN6 cells in the presence of supernatants derived from iBMDM cells transfected with poly(I:C) (PIC), a viral mimic. This exposure led to an upregulation of ISG15 expression in MIN6 cells, which was accompanied by the suppression of their functional capabilities and viability. Intriguingly, the direct transfection of MIN6 cells with PIC increased the expression of ISG15. We further found that elevated levels of ISG15 had a direct inhibitory effect on insulin secretion and it also contributed to β-cell apoptosis in a TNF-α-dependent manner. In conclusion, our study revealed a potential underlying mechanism through which ISG15 increases the apoptosis of β-cells, providing valuable insights that could facilitate the development of T1D treatment strategies.
研究领域:
免疫学
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内分泌学
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糖尿病学
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DOI
PubMed
高影响因子
JOURNAL OF THE WORLD AQUACULTURE SOCIETY
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2016
·Vol. 48
·期 2
·360-373
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IF 0.665
Jing Qian,Chunhua Ren,Jianjun Xia,Zonghe Yu,Chaoqun Hu
Alpha-2-macroglobulin (A 2 M) is essential for hosts defending against pathogen infections. In this study, two distinct A 2 Ms were identified from sea cucumbers Stichopus monotuberculatus and Holothuria atra , which belong to different genera in the Phylum Echinodermata, and named StmA 2 M and HaA 2 M, respectively. Structural analysis of StmA 2 M and HaA 2 M revealed that all contain the bait region domain, thioester domain, and receptor-binding domain. Phylogenetic analysis indicated that StmA 2 M and HaA 2 M all belong to the echinoderm A 2 Ms. The cleavage site RXXR and the catalytic histidine residue for complement component C3 were found in StmA 2 M and HaA 2 M. Compared with human A 2 M, the three-dimensional structures of StmA 2 M and HaA 2 M were more similar to that of common carp A 2 M. Both StmA 2 M and HaA 2 M showed the strongest response at transcriptional levels to lipopolysaccharide (LPS) at 12 h and polyriboinosinic polyribocytidylic acid [Poly (I: C)] at 24 h, respectively. Activity of StmA 2 M showed the strongest response to Poly (I: C) at 6 h, while the strongest change of HaA 2 M activity was induced by LPS at 24 h. The differential mRNA expression and enzyme activity levels suggested that A 2 M in sea cucumbers might be involved in different immune responses to LPS or Poly (I: C) challenge.
研究领域:
海洋生物学
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免疫学
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分子生物学
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基因组学
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DOI
高影响因子
Frontiers in Immunology
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2025
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IF 5.9
Dong-Ni Pei,Yang Song,Ying-Xia Zhou,Bo Shu,Shao-wei Huang,Fa-Zhao Li,Wei-Dong Dai,Bao-Ye Sun
Purpose Conventional type 1 dendritic cells (cDC1s) mastermind anti-cancer immunity and play a pivotal role in determining the efficacy of cancer immunotherapies. In this study, we sought to decipher the dynamic changes in the tumor immune landscape during intrahepatic cholangiocarcinoma (iCCA) development and harness the therapeutic potential of targeting cDC1s for cancer therapy. Methods We constructed spontaneous murine iCCAs via hydrodynamic tail vein injection (HDTVi) of plasmids encoding AKT/YAP. To characterize tumor-infiltrating immune cell populations throughout iCCA carcinogenesis and progression, we performed time-of-flight mass cytometry (CyTOF). To expand and activate cDC1s, we combined Flt3L with poly I:C (FL-pIC) therapy and assessed its therapeutic efficacy in both AKT/YAP-induced iCCAs and a subcutaneous tumor injection model. Flow cytometric analyses were used to evaluate intra-tumoral infiltration levels of cDCs and CD8 + T cells. Results CyTOF analysis revealed the progressive formation of an immunosuppressive tumor microenvironment as iCCA advances. Crucially, infiltration of cDC1s dramatically decreases in advanced iCCAs compared to early-stage tumors. Combined FL-pIC therapy preferentially expanded CD103 + cDC1s, powerfully inhibiting tumorigenesis in AKT/YAP-driven murine iCCAs and sensitizing these tumors to anti-PD-1 therapy. Moreover, FL-pIC therapy markedly suppressed the growth of established mIC-23 subcutaneous tumors. Conclusions Our findings demonstrate that recruiting and activating intra-tumoral cDC1s is feasible and essential for driving anti-tumor CD8 + T cell immune responses and enhancing anti-PD-1 therapeutic effectiveness in iCCA.
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高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
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2021
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IF 3.636
Feng-Ying Gao,Xin Zhou,Mai-Xin Lu,Miao Wang,Zhi-Gang Liu,Jian-Meng Cao,Xiao-Li Ke,Meng-Meng Yi,Deng-Gao Qiu
Toll-like receptors (TLRs) play a critical role in the innate immune response of fish. In this study, we isolated the cDNA sequence of Nile tilapia TLR1 ( On TLR1). The deduced OnTLR1 protein contains a signal peptide , 7 leucine-rich repeats (LRRs), a C-terminal LRR (LRR-CT), a transmembrane region and a highly conserved TIR domain. In healthy Nile tilapia, the On TLR1 transcript was broadly expressed in all examined tissues, with the highest expression levels in the spleen . After infection with Streptococcus agalactiae , the On TLR1 transcripts were upregulated in the gill and kidney. After stimulation with polyinosinic-polycytidylic acid (poly(I:C)), the expression levels of On TLR1 were significantly downregulated in the intestine , whereas On TLR1 transcripts were significantly upregulated in the kidney. After challenge with lipopolysaccharide (LPS), the expression levels of On TLR1 were significantly upregulated in the spleen and kidney. The subcellular localization showed that On TLR1 was expressed in the cytoplasm. TLR1 significantly increased MyD88-dependent NF-κB activity. However, the results of a pull-down assay showed that On TLR1 did not interact with MyD88 or TIRAP. Binding assays revealed the specificity of OnTLR1 for pathogen-associated molecular patterns (PAMPs) and bacteria that included S. agalactiae , Aeromonas hydrophila and poly(I:C) and LPS. Taken together, these findings suggest that OnTLR1, as a pattern recognition receptor (PRR), might play an important role in the immune response to pathogen invasion.
研究领域:
免疫学
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分子生物学
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鱼类生物学
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病原识别
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DOI
PubMed
高影响因子
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