Immunology最新文献

Coexistence of IL12Rβ1 and BTK Mutations in a Family. 一个家族中同时存在 IL12Rβ1 和 BTK 基因突变

IF 4.9 3区医学

Immunology Pub Date : 2024-10-30 DOI: 10.1111/imm.13874

Hulya Kose, Orhan Gorukmez, Sara Sebnem Kilic

引用次数: 0

Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. 癌症中的代谢重编程：对免疫抑制微环境的影响

IF 4.9 3区医学

Immunology Pub Date : 2024-10-27 DOI: 10.1111/imm.13871

Durre Aden, Niti Sureka, Samreen Zaheer, Jai Kumar Chaurasia, Sufian Zaheer

引用次数: 0

Sphingosine-1-Phosphate Signalling Inhibition Suppresses Th1-Like Treg Generation by Reversing Mitochondrial Uncoupling. 鞘氨醇-1-磷酸信号抑制通过逆转线粒体解偶联抑制 Th1 类 Treg 的生成

IF 4.9 3区医学

Immunology Pub Date : 2024-10-24 DOI: 10.1111/imm.13870

Rachel Coulombeau, Claudia Selck, Nicolas Giang, Abdulrahman Al-Mohammad, Natalie Ng, Allison K Maher, Rafael Argüello, Antonio Scalfari, James Varley, Richard Nicholas, Margarita Dominguez-Villar

{"title":"Sphingosine-1-Phosphate Signalling Inhibition Suppresses Th1-Like Treg Generation by Reversing Mitochondrial Uncoupling.","authors":"Rachel Coulombeau, Claudia Selck, Nicolas Giang, Abdulrahman Al-Mohammad, Natalie Ng, Allison K Maher, Rafael Argüello, Antonio Scalfari, James Varley, Richard Nicholas, Margarita Dominguez-Villar","doi":"10.1111/imm.13870","DOIUrl":"https://doi.org/10.1111/imm.13870","url":null,"abstract":"Inflammatory environments induce the generation of dysfunctional IFNγ+T-bet+FOXP3+ Th1-like Tregs, which show defective function and are found in autoimmune conditions including multiple sclerosis (MS). The pathways that control the generation of Th1-like Tregs are not well understood. Sphingosine-1-phosphate (S1P) signalling molecules are upregulated in Th1-like Tregs, and in vivo S1P inhibition with Fingolimod (FTY720) inhibits the expression of genes responsible for Treg plasticity in MS patients. However, the underlying mechanisms are unknown. Here we show that S1P signalling inhibition by FTY720 inhibits the generation of Th1-like Tregs and rescues their suppressive function. These effects are mediated by a decrease in mTORC1 signalling and reversal of the mitochondrial uncoupling that Tregs undergo during their reprogramming into Th1-like Tregs in vitro. Finally, these results are validated in in vivo-generated Th1-like Tregs, as Tregs from MS patients treated with FTY720 display decreased Th1-like Treg frequency, increased suppressive function and mitochondrial metabolism rebalance. These results highlight the involvement of mitochondrial uncoupling in Treg reprogramming and identify S1P signalling inhibition as a target to suppress the generation of dysfunctional Th1-like Tregs.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RGS10 Deficiency Alleviated Intestinal Mucosal Inflammation Through Suppression of Th1/Th17 Cell Immune Responses in Ulcerative Colitis. RGS10 缺陷通过抑制溃疡性结肠炎患者的 Th1/Th17 细胞免疫反应缓解肠粘膜炎症

IF 4.9 3区医学

Immunology Pub Date : 2024-10-20 DOI: 10.1111/imm.13869

Yonghong Yang, Yiming Shao, Xizhuang Gao, Zongjing Hu, Yan Wang, Cuimei Ma, Guiyuan Jin, Fengqin Zhu, Guanjun Dong, Guangxi Zhou

{"title":"RGS10 Deficiency Alleviated Intestinal Mucosal Inflammation Through Suppression of Th1/Th17 Cell Immune Responses in Ulcerative Colitis.","authors":"Yonghong Yang, Yiming Shao, Xizhuang Gao, Zongjing Hu, Yan Wang, Cuimei Ma, Guiyuan Jin, Fengqin Zhu, Guanjun Dong, Guangxi Zhou","doi":"10.1111/imm.13869","DOIUrl":"https://doi.org/10.1111/imm.13869","url":null,"abstract":"Regulator of G-protein signalling (RGS) 10 plays critical roles in several immune related diseases. However, whether RGS10 is involved in colonic inflammation of ulcerative colitis (UC) is still obscure. This study aimed to investigate the role of RGS10 in UC. In this study, RGS10 expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and immunofluorescent analysis. Single-cell RNA sequencing of intestinal mucosa was performed to identify key immune cells with differentially expressed RGS10. RGS10 knockout mice were generated and established dextran sulphate sodium (DSS)-induced colitis. Expression of inflammatory cytokines on mRNA and protein levels was detected by qRT-PCR, enzyme-linked immunosorbent assay, and flow cytometry. We found that RGS10 expression was significantly elevated in UC patients, especially in CD4+ T cells, compared with healthy subjects. Intriguingly, RGS10 deficiency markedly alleviated DSS-induced colitis and decreased the proportion of Th1 and Th17 cells in lamina propria mononuclear cells (LPMCs), peripheral blood (PB), spleens, and mesenteric lymph nodes (mLNs). Mechanistically, RGS10 deficiency blocked the differentiation of Th1 and Th17 cells by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT3. The co-immunoprecipitation analysis further showed that RGS10 could interact with protein tyrosine phosphatase non-receptor type 2 (PTPN2), and further regulated Th1 and Th17 cells differentiation of CD4+ T cells. In conclusion, RGS10 deficiency alleviated intestinal mucosal inflammation through inhibition of Th1/Th17 cell-mediated immune responses via interaction with PTPN2 in CD4+ T cells. Therefore, targeting RGS10 may represent a novel therapeutic approach for UC treatment.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Immune Regulatory Functions in B Cells Are Restored by CpG to Reduce Experimental Food Allergy. CpG可恢复B细胞的免疫调节功能，减轻实验性食物过敏。

IF 4.9 3区医学

Immunology Pub Date : 2024-10-09 DOI: 10.1111/imm.13868

Qiao Liu, Dong-Hua Bin, Zhuo-Ya Wang, Ke-Ping Peng, Wang Tang, Jing-Weng Huang, Ling-Zhi Xu, Xiang-Yu Wang, Ping-Chang Yang, Gui-Xiang Tian

{"title":"The Immune Regulatory Functions in B Cells Are Restored by CpG to Reduce Experimental Food Allergy.","authors":"Qiao Liu, Dong-Hua Bin, Zhuo-Ya Wang, Ke-Ping Peng, Wang Tang, Jing-Weng Huang, Ling-Zhi Xu, Xiang-Yu Wang, Ping-Chang Yang, Gui-Xiang Tian","doi":"10.1111/imm.13868","DOIUrl":"https://doi.org/10.1111/imm.13868","url":null,"abstract":"Dysfunctional immune regulation contributes to the pathogenesis of food allergy (FA). The mechanism behind regulatory B-cell dysfunction is unclear. CpG has immune regulatory functions. The purpose of this study is to use CpG to recover the immune suppressive functions of B cells in mice with FA. An FA mouse model was created using ovalbumin as the specific antigen. Flow cytometry was used to isolate B cells from the intestinal tissues. The immune regulatory functions of B cells were assessed using immunological approaches. The results showed that the FA response was linked to low IL-10 levels in gut lavage fluids of FA mice. FA mouse intestinal B cells produced lower amounts of IL-10 as compared with B cells isolated from naïve control mice. Impaired immune suppressive functions were observed in B cells isolated from the FA mouse intestine. The inducibility of the Il10 expression in naïve B cells of the intestine of FA mice was defective. The induction of Il10 expression in FA B cells could be restored by CpG through regulating the methylation status of the Cmip promoter. CpG promoted the therapeutic efficacy of allergen specific immunotherapy by restoring the induction of IL-10+ B cells in the intestine. The expression of Il10 in B cells of the FA mouse intestine was impaired. Administration of CpG could restore the expression of Il10 in B cells in the intestine and promote immunotherapy for FA.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Helios-Illuminating the way for lymphocyte self-control. 太阳神--照亮淋巴细胞自我控制之路

IF 4.9 3区医学

Immunology Pub Date : 2024-10-01 DOI: 10.1111/imm.13866

Iivo Hetemäki, T Petteri Arstila, Eliisa Kekäläinen

{"title":"Helios-Illuminating the way for lymphocyte self-control.","authors":"Iivo Hetemäki, T Petteri Arstila, Eliisa Kekäläinen","doi":"10.1111/imm.13866","DOIUrl":"https://doi.org/10.1111/imm.13866","url":null,"abstract":"Transcription factor Helios, encoded by the IKZF2 gene, has an important role in regulatory T cells by stabilizing their suppressive phenotype. While Helios is prominently expressed in regulatory T cells, its expression extends beyond to include effector T cells, follicular regulatory T cells, B cells, and innate-like lymphocyte populations. Recent characterizations of patients with inborn error of immunity due to damaging IKZF2 variants coupled with translational research on lymphocytes from healthy individuals, have increased our understanding on Helios' multifaceted role in controlling the human adaptive immune system. A less studied role for Helios beyond the stabilizing of regulatory T cells has emerged in directing effector T cell maturation. In the absence of functional Helios, effector T cells acquire more inflammatory phenotype and are prone to senescence. Loss of Helios expression disrupts the regulation of the germinal centre reaction, often resulting in either hypogammaglobulinemia or B cell autoimmunity. This review summarizes findings from studies in both mice and men offering a comprehensive understanding of the impact of the transcription factor Helios on the adaptive immune system.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of type I interferon signalling pathway by urate in primary human PBMCs. 尿酸盐下调原代人类 PBMC 的 I 型干扰素信号通路。

IF 4.9 3区医学

Immunology Pub Date : 2024-10-01 DOI: 10.1111/imm.13858

Medeea Badii, Valentin Nica, Ancuța R Straton, Brenda Kischkel, Orsolya Gaal, Georgiana Cabău, Viola Klück, Ioana Hotea, Boris Novakovic, Cristina Pamfil, Simona Rednic, Mihai G Netea, Radu A Popp, Leo A B Joosten, Tania O Crișan

{"title":"Downregulation of type I interferon signalling pathway by urate in primary human PBMCs.","authors":"Medeea Badii, Valentin Nica, Ancuța R Straton, Brenda Kischkel, Orsolya Gaal, Georgiana Cabău, Viola Klück, Ioana Hotea, Boris Novakovic, Cristina Pamfil, Simona Rednic, Mihai G Netea, Radu A Popp, Leo A B Joosten, Tania O Crișan","doi":"10.1111/imm.13858","DOIUrl":"https://doi.org/10.1111/imm.13858","url":null,"abstract":"Type I interferons (IFN1s) mediate innate responses to microbial stimuli and regulate interleukin (IL)-1 and IL-1 receptor antagonist (Ra) production in human cells. This study explores interferon-stimulated gene (ISG) alterations in the transcriptome of patients with gout and stimulated human primary cells in vitro in relation to serum urate concentrations. Peripheral blood mononuclear cells (PBMCs) and monocytes of patients with gout were primed in vitro with soluble urate, followed by lipopolysaccharide (LPS) stimulation. Separately, PBMCs were stimulated with various toll-like receptor (TLR) ligands. RNA sequencing and IL-1Ra cytokine measurement were performed. STAT1 phosphorylation was assessed in urate-treated monocytes. Cytokine responses to IFN-β were evaluated in PBMCs cultured with or without urate and restimulated with LPS and monosodium urate (MSU) crystals. Transcriptomics revealed suppressed IFN-related signalling pathways in urate-exposed PBMCs or monocytes which was supported by diminishment of phosphorylated STAT1. The stimulation of PBMCs with IFN-β did not modify the urate-induced inflammation. Interestingly, in vivo, serum urate concentrations were inversely correlated to in vitro ISG expression upon stimulations with TLR ligands. These findings support a deficient IFN1 signalling in the presence of elevated serum urate concentrations, which could translate to increased susceptibility to infections.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New Engineered-Chimeric Botulinum Neurotoxin Mutant Acts as an Effective Bivalent Vaccine Against Botulinum Neurotoxin Serotype A and E. 新设计的嵌合型肉毒杆菌神经毒素突变体可作为针对肉毒杆菌神经毒素血清型 A 和 E 的有效双价疫苗

IF 4.9 3区医学

Immunology Pub Date : 2024-10-01 DOI: 10.1111/imm.13867

Jingrong Wang, Jiansheng Lu, Bolin Li, Xiaoyu Liu, Rong Wang, Peng Du, Shuo Yu, Zhixin Yang, Yunzhou Yu

{"title":"New Engineered-Chimeric Botulinum Neurotoxin Mutant Acts as an Effective Bivalent Vaccine Against Botulinum Neurotoxin Serotype A and E.","authors":"Jingrong Wang, Jiansheng Lu, Bolin Li, Xiaoyu Liu, Rong Wang, Peng Du, Shuo Yu, Zhixin Yang, Yunzhou Yu","doi":"10.1111/imm.13867","DOIUrl":"https://doi.org/10.1111/imm.13867","url":null,"abstract":"Botulinum neurotoxins (BoNTs), including serotypes A and E, are potent biotoxins known to cause human poisoning. In addition to the critical protective antigen found in the full BoNT molecule, the receptor binding domain (Hc domain), BoNTs also harbour another essential protective antigen-the light chain-translocation domain (L-HN domain). Leveraging these pivotal protective antigens, we genetically engineered a series of inactivated chimeric molecules incorporating L-HN and Hc domains of BoNT/A and E. The structure of these chimeric molecules, mirror BoNT/A and E, but are devoid of enzyme activity. Experimental findings demonstrated that a lead candidate mEL-HN-mAHc harnessing the inactivated protease LCHN/E with the mutated gangliosides binding site Hc/A (mE-mA) elicited robust immune protection against BoNT/A and E simultaneously in a mouse model, requiring low immune dosages and minimal immunisations. Moreover, mE-mA exhibited high protective efficacy against BoNT/A and E in guinea pigs and New Zealand white rabbits, resulting in elevated neutralising antibody titres. Furthermore, mE-mA proved to be a more stable and safer vaccine compared to formaldehyde-inactivated toxoid. Our data underscore the genetically engineered mE-mA as a highly effective bivalent vaccine against BoNT/A and E, paving the way for the development of polyvalent vaccines against biotoxins.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How maternal factors shape the immune system of breastfed infants to alleviate food allergy: A systematic and updated review. 母体因素如何塑造母乳喂养婴儿的免疫系统以缓解食物过敏：系统性最新综述。

IF 4.9 3区医学

Immunology Pub Date : 2024-09-30 DOI: 10.1111/imm.13864

Yuhong Wu, Bihua Chen, Huan Wu, Jinyan Gao, Xuanyi Meng, Hongbing Chen

{"title":"How maternal factors shape the immune system of breastfed infants to alleviate food allergy: A systematic and updated review.","authors":"Yuhong Wu, Bihua Chen, Huan Wu, Jinyan Gao, Xuanyi Meng, Hongbing Chen","doi":"10.1111/imm.13864","DOIUrl":"https://doi.org/10.1111/imm.13864","url":null,"abstract":"What infants eat early in life may shape the immune system and have long-standing consequences on the health of the host during later life. In the early months post-birth, breast milk serves as the exclusive and optimal nourishment for infants, facilitating crucial molecular exchanges between mother and infant. Recent advances have uncovered that some maternal factors influence breastfed infant outcomes, including the risk of food allergy (FA). To date, accumulated data show that breastfed infants have a lower risk of FA. However, the issue remains disputed, some reported preventive allergy effects, while others did not confirm such effects, or if identified, protective effects were limited to early childhood. The disputed outcomes may be attributed to the maternal status, as it determines the compounds of the breast milk that breastfed infants are exposed to. In this review, we first detail the compounds in breast milk and their roles in infant FA. Then, we present maternal factors resulting in alterations in breast milk compounds, such as maternal health status, maternal diet intake, and maternal food allergen intake, which subsequently impact FA in breastfed infants. Finally, we analyze how these compounds in breast milk alleviated the infant FA by mother-to-infant transmission. Altogether, the mechanisms are primarily linked to the synergetic and direct effects of compounds in breast milk, via promoting the colonization of gut microbiota and the development of the immune system in infants.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA technology and nanocarriers empowering in vivo chimeric antigen receptor therapy 为体内嵌合抗原受体疗法赋能的 RNA 技术和纳米载体。

IF 4.9 3区医学

Immunology Pub Date : 2024-09-28 DOI: 10.1111/imm.13861

Jingsheng Cai, Shaoyi Chen, Zheng Liu, Haoran Li, Peiyu Wang, Fan Yang, Yun Li, Kezhong Chen, Ming Sun, Mantang Qiu

引用次数: 0