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关键词： Trogocytosis   CD8+CD45RC low   Regulatory T cells   Plasmacytoid dendritic cells   Immune tolerance  

摘要： Objective: Donor-specific suppression by MHC-II+CD8+CD45RClow/-regulatory T cells (Tregs) was observed in our prior study, here we endeavor to investigate the mechanism underlying generation of the MHCII+CD8+CD45RClow/-Tregs. Methods: The presence of MHC-II+CD8+CD45RClow/-Tregs within tolerated grafts was confirmed using a multicolor immunofluorescence technique in spontaneous tolerant rat liver transplant model. We aimed to elucidate the generation mechanism of MHC-II+CD8+CD45RClow/-Tregs by purifying naive CD8+CD45RClow/-Tregs and plasmacytoid dendritic cells (pDCs) from recipients and co-culturing them to induce trogocytosis. Initially, we examined the immunophenotype and cytokine secretion of MHC-II+CD8+CD45RClow/-Treg using flow cytometry. Trogocytosis of peptide-MHC class II complexes was visualized using a confocal microscope. Subsequently, we analyzed the donor-specific inhibitory effect of MHC-II+CD8+CD45RClow/-Tregs using CFSE-based lymphocyte proliferation analysis. Finally, we explored the possible transfer mechanisms of MHC class II using IFN-gamma stimulation and 1-MT to block indoleamine-(2,3)-dioxygenase (IDO). Results: In the spontaneously tolerant rat liver transplants, MHC-II+CD8+CD45RClow/-Tregs and IL-10 expression were upregulated. Our in vitro study revealed that trogocytosis occurring between naive CD8+CD45RClow/-Tregs and pDCs could induce MHC-II+CD8+CD45RClow/-Tregs. The semi-direct pathway represents the primary mode of Trogocytosis-mediated transfer of MHC-II molecules from pDCs to CD8+CD45RClow/-Tregs. The MHCII+CD8+CD45RClow/-Tregs exhibited high secretion of IL-10 and IFN-gamma. Co-culturing with MHCII+CD8+CD45RClow/-Tregs significantly suppressed the proliferation of CD4+CD25-effector T cells. Moreover, this inhibitory effect was donor-specific and could be overcome in the presence of third-party antigen-presenting cells. Our data also suggested that blocking the IFN-gamma/IDO signaling pathway could inhibit the generation of trogocyt

摘要： [Erratum to: BMB Reports 2025; 58(7): 307-312, PMID: 40495489, PMCID: PMC12313400] BMB Reports recently published the article "Modulating CD226 and PD-(L)1 pathways improves CMV-specific CD8＋T cell responses in the absence of IL-2" (BMB Rep. 2025; Vol. 58, No.7, pp.307-312) by Hye-In Sim et al. The original publication inadvertently omitted two sections: ACKNOWLEDGMENTS and CONFLICT OF INTEREST. These sections have now been added to the online version. The authors and editorial office apologize for any inconvenience or confusion this omission may have caused to the authors and readers. ACKNOWLEDGMENTS This work was supported by an intramural grant from KIST and Asan Medical Center (2022IP0092-1) and by grants from the National Research Foundation of Korea (NRF) (RS-2024-00338729 to H. Jin and RS-2024-00337093 to Y. Park). CONFLICT OF INTEREST All authors declare that they have no competing interests.

关键词： Curcumin   HPSE   Colorectal cancer   IL-6-STAT5 axis   Non-coding RNAs  

摘要： Our previous research demonstrated that curcumin suppresses mouse colorectal cancer (CRC) cell CT26 migration and invasion by inhibiting heparanase (HPSE) mRNA expression. To further elucidate the mechanism of curcumin in human CRC treatment, we hypothesized that HPSE plays a pivotal role in human CRC metastasis and that curcumin inhibits this process by downregulating HPSE expression through epigenetic regulation mediated by non-coding RNAs. For further research, human CRC cells were infected with lentivirus to establish overexpression of HPSE cell lines and corresponding negative control cell lines. In vitro and in vivo experiments showed that curcumin inhibited the proliferation, migration, and metastasis of CRC cancer by inhibiting HPSE expression. In the tumor microenvironment, HPSE played an important role in activating the IL-6/STAT5 axis signaling pathway by destructing the extracellular matrix and releasing large number of cytokines, while changing the tumor microenvironment and EMT process, thus promoting tumor metastasis. RNA-seq analysis combined with qRT-PCR results showed that curcumin's inhibition of HPSE expression involved the regulation of non-coding RNAs. Taken together, our results suggested that HPSE promotes CRC metastasis by activating the IL-6/STAT5 signaling axis, disrupting the ECM, releasing cytokines, and altering the tumor microenvironment to facilitate EMT. Curcumin significantly inhibits CRC cell proliferation, migration, and metastasis by downregulating HPSE expression via non-coding RNAs, which related to IL-6/STAT5 axis signal pathways. This research provides a comprehensive understanding of the molecular mechanisms underlying curcumin's anti-CRC effects, emphasizing the role of HPSE and non-coding RNAs in tumor metastasis. These findings pave the way for the development of novel therapeutic strategies targeting HPSE and its regulatory pathways in CRC.

关键词： IL-10   aTCMR   NFATc1 signaling pathway   T cell   Kidney transplantation  

摘要： The cause of acute T cell-mediated rejection (aTCMR) is believed to be immune hyperfunction of T cells after kidney transplantation. Nowadays, calcineurin inhibitors are widely used to inhibit the proliferation of T cells when aTCMR occurs. However, the therapeutic dose window of these drugs is relatively narrow and long time use of these drugs may lead to serious side effects. Besides, whether IL-10, a new immune tolerance mediator, playing a therapeutic role on aTCMR remains unclear. The level of IL-10 decreased in patients with aTCMR, suggesting that IL-10 may be involved in the progression of aTCMR. IL-10 could inhibit the proliferation and metabolism of T cells in vitro and in vivo, accompanied by reducing the levels of IL-2, IFN-gamma, and TNF-alpha. Moreover, we confirmed that IL-10 exerts immunosuppressive effects by inhibiting the NFATc1 signaling pathway of T cells. This viewpoint may provide a new therapeutic idea for clinical application.

关键词： HLA‐B*44   NGS   novel allele  

摘要： Four new HLA-B*44 alleles characterised by Next Generation Sequencing, HLA-B*44:431Q, -B*44:432Q, -B*44:433 and -B*44:434.

关键词： biopolymer   IL-12   immunotherapy   elastin-like polypeptide  

摘要： Despite renewed interest in IL-12 as a cancer immunotherapy due to its ability to stimulate the adaptive immune system, its short half-life and narrow therapeutic window continues to present challenges for effective delivery. Previous studies with IL-12 have investigated the effects of route of delivery or sustained delivery of the cytokine on its efficacy but are unable to simultaneously investigate the effects of both within the same system. This work seeks to address this gap by utilizing an elastin-like polypeptide (ELP) carrier, which can undergo a thermally triggered phase transition to a gel-like depot, to probe the effects of both sustained release and spatial delivery of IL-12. By conjugating IL-12 with an ELP, this work creates an IL-12-ELP fusion that can be injected intratumorally or subcutaneously to form a sustained-release depot. In a B16F10 murine model, intratumoral injection of a depot-forming IL-12-ELP fusion significantly improved survival compared to free IL-12. IL-12-ELP is retained within the tumor approximately fourfold longer than free IL-12, resulting in higher CD8+ T cell recruitment at the tumor and local concentrations of inflammatory cytokines at Day 2. Taken together, this work provides insights into rational cytokine delivery, the importance of tumor localization, and the benefits of sustained release.

关键词： HLA‐A   HLA‐B   HLA‐C   NGS   novel allele  

摘要： Nine novel HLA alleles were detected during the HLA typing process.

关键词： Peritoneal dialysis   Peritoneal equilibration test   Peritoneal solute transport rate   Cytokine   IL-8  

摘要： Background: Several cytokine levels in dialysate, particularly interleukin-6 (IL-6), have been investigated as potential biomarkers for peritoneal solute transport rate (PSTR). However, studies examining the relationship between systemic cytokine levels and PSTR have yielded contradictory results. In this study, we aimed to assess 12 kinds of cytokines in serum and explore their potential relationship with peritoneal transport function. Methods: Patients undergoing peritoneal dialysis (PD) from September 2022 to September 2024 were retrospectively analyzed at our PD center. The patients were categorized into fast and non-fast PSTR groups based on the 4-h dialysate creatinine /plasma creatinine ratio (D/P Cr). The systemic levels of 12 cytokines (IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17 A, TNF-alpha, IFN-alpha, and IFN-gamma) in both groups were measured using flow cytometry and compared. The relationship between serum cytokine levels and baseline peritoneal transport status was analyzed by univariate and multivariate logistic regression analyses. Results: A total of 284 patients were enrolled in this study. According to the D/P Cr, 171 patients (60.2 %) were classified as non-fast PSTR group, while 113 patients (39.8 %) were classified as fast PSTR group. Among the 12 cytokines analyzed, serum IL-8 exhibited a significant difference between the two groups (P = 0.01). IL-8/IL-10 and IL-12p70/IL-10 ratios were also significantly higher in fast PSTR group. In the subgroup of incident PD patients, multivariate analysis revealed that total cholesterol (OR 0.559, 95 % CI 0.323-0.966, P = 0.037) and serum IL-8 (OR 1.040, 95 % CI 1.006-1.075, P = 0.021) were significantly and independently associated with baseline fast PSTR. Conclusion: The systemic IL-8 level is positively correlated with PSTR in patients undergoing PD, which may serve as an indicator of baseline peritoneal transport function.