Immune Network最新文献

Sphingosylphosphorylcholine Promotes Th9 Cell Differentiation Through Regulation of Smad3, STAT5, and β-Catenin Pathways. 鞘甲磷胆碱通过调控Smad3、STAT5和β-Catenin通路促进Th9细胞分化。

IF 4.3 4区医学

Immune Network Pub Date : 2024-12-26 eCollection Date: 2024-12-01 DOI: 10.4110/in.2024.24.e45

Ji Cheol Kim, Wonseok Hu, Mingyu Lee, Geon Ho Bae, Ji Ye Park, Suh Yeon Lee, Yu Sun Jeong, Byunghyun Park, Joon Seong Park, Brian A Zabel, Yong-Soo Bae, Yoe-Sik Bae

{"title":"Sphingosylphosphorylcholine Promotes Th9 Cell Differentiation Through Regulation of Smad3, STAT5, and β-Catenin Pathways.","authors":"Ji Cheol Kim, Wonseok Hu, Mingyu Lee, Geon Ho Bae, Ji Ye Park, Suh Yeon Lee, Yu Sun Jeong, Byunghyun Park, Joon Seong Park, Brian A Zabel, Yong-Soo Bae, Yoe-Sik Bae","doi":"10.4110/in.2024.24.e45","DOIUrl":"10.4110/in.2024.24.e45","url":null,"abstract":"Sphingosylphosphorylcholine (SPC) is one of sphingomyelin-derived sphingolipids. SPC levels are increased in ascitic fluids of ovarian cancer patients and stratum corneum of atopic dermatitis (AD) patients. SPC has antitumor activity against several cancer cells by reducing proliferation and migration and increasing apoptosis in vitro. SPC can also cause scratching, potentially exacerbating symptoms of AD. However, the role of SPC in modulating immune responses, particularly in the differentiation of Th9 cells, which carry the most powerful antitumor activity among CD4+ T cells, has yet to be investigated. In this study, we found that SPC is another inducer of Th9 cell differentiation by replicating TGF-β. SPC upregulated Smad3, STAT5, and β-catenin signaling pathways. Increased Smad3 and STAT5 signaling pathways by SPC promoted the differentiation of Th9 cells and increased β-catenin signaling pathway resulted in a less-exhausted, memory-like phenotype of Th9 cells. Increased Smad3, STAT5 and β-catenin signaling pathways by SPC were mediated by increased mitochondrial ROS. These results suggest that SPC is an important endogenous inducer of Th9 cell differentiation and may be one of the targets for treating Th9-related diseases, and that enhancing Th9 differentiation by SPC may be helpful in adoptive T cell therapy for cancer treatment.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 6","pages":"e45"},"PeriodicalIF":4.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activation of Immune Responses Through the RIG-I Pathway Using TRITC-Dextran Encapsulated Nanoparticles. tritc -葡聚糖封装纳米颗粒通过RIG-I途径激活免疫反应。

IF 4.3 4区医学

Immune Network Pub Date : 2024-12-24 eCollection Date: 2024-12-01 DOI: 10.4110/in.2024.24.e44

Hayeon Baek, Seung-Woo Yang, Min-Kyung Kim, Dongwoo Kim, Chaeyeon Lee, Seulki Kim, Yunseok Lee, Min Park, Han-Sung Hwang, Hyun-Jong Paik, Young-Sun Kang

{"title":"Activation of Immune Responses Through the RIG-I Pathway Using TRITC-Dextran Encapsulated Nanoparticles.","authors":"Hayeon Baek, Seung-Woo Yang, Min-Kyung Kim, Dongwoo Kim, Chaeyeon Lee, Seulki Kim, Yunseok Lee, Min Park, Han-Sung Hwang, Hyun-Jong Paik, Young-Sun Kang","doi":"10.4110/in.2024.24.e44","DOIUrl":"10.4110/in.2024.24.e44","url":null,"abstract":"Pathogen-associated molecular patterns (PAMPs) are highly conserved motifs originating from microorganisms that act as ligands for pattern recognition receptors (PRRs), which are crucial for defense against pathogens. Thus, PAMP-mimicking vaccines may induce potent immune activation and provide broad-spectrum protection against microbes. Dextran encapsulation can regulate the surface characteristics of nanoparticles (NPs) and induces their surface modification. To determine whether dextran-encapsulated NPs can be used to develop antiviral vaccines by mimicking viral PAMPs, we synthesized NPs in a cyclohexane inverse miniemulsion (Basic-NPs) and further encapsulated them with dextran or tetramethylrhodamine isothiocyanate (TRITC)-dextran (Dex-NPs or TDex-NPs). We hypothesized that these dextran encapsulated NPs could activate innate immunity through cell surface or cytosolic PRRs. In vitro and in vivo experiments were performed using RAW 264.7 and C57BL/6 mice to test different concentrations and routes of administration. Only TDex-NPs rapidly increased retinoic acid-inducible gene I (RIG-I) at 8 h and directly bound to it, producing 120-300 pg/ml of IFN-α via the ERK/NF-κB signaling pathway in both in vitro and in vivo models. The effect of TDex-NPs in mice was observed exclusively with footpad injections. Our findings suggest that TRITC-dextran encapsulated NPs exhibit surface properties for RIG-I binding, offering potential development as a novel antiviral and anticancer RIG-I agonist.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 6","pages":"e44"},"PeriodicalIF":4.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Monovalent Anti-CD3 Antibodies Effectively Eliminate the TCR-Positive Fraction of TCR-Deleted Allogeneic CAR-T Cells to Prevent GVHD. 单价抗cd3抗体有效消除tcr缺失的异体CAR-T细胞中tcr阳性部分以预防GVHD

IF 4.3 4区医学

Immune Network Pub Date : 2024-12-24 eCollection Date: 2024-12-01 DOI: 10.4110/in.2024.24.e43

Ji Hwan Kim, Hyori Kim, A-Neum Lee, Hyung Bae Park, Kyungho Choi

{"title":"Monovalent Anti-CD3 Antibodies Effectively Eliminate the TCR-Positive Fraction of TCR-Deleted Allogeneic CAR-T Cells to Prevent GVHD.","authors":"Ji Hwan Kim, Hyori Kim, A-Neum Lee, Hyung Bae Park, Kyungho Choi","doi":"10.4110/in.2024.24.e43","DOIUrl":"10.4110/in.2024.24.e43","url":null,"abstract":"Chimeric antigen receptor-transduced T (CAR-T) cell therapy is an effective cell therapy against advanced hematological tumors. However, the use of autologous T cells limits its timely and universal generation. Allogeneic CAR-T cell therapy may be a good alternative as a ready-to-use therapeutic. Graft-versus-host disease (GVHD) is an obstacle for allogeneic CAR-T cells, but can be prevented by TCR deletion through genome editing. However, the remaining TCR-positive cells must be eliminated by costly, large-scale magnetic cell separation. Therefore, an alternative method for removing TCR-positive cells is needed. In this study, we found that monovalent anti-CD3 Abs such as Fab and single-chain variable fragment (scFv), but not whole IgG, induce apoptosis of in vitro expanded T cells, thereby effectively depleting residual TCR-positive T cells during TCR-deleted CAR-T cell generation and ultimately preventing xenogeneic GVHD in vivo. Thus, monovalent anti-CD3 treatment during allogeneic CAR-T cell manufacturing would be an efficient method to prevent GVHD.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 6","pages":"e43"},"PeriodicalIF":4.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

T Cell Resistance: On the Mechanisms of T Cell Non-activation. T细胞耐药：论T细胞非活化机制

IF 4.3 4区医学

Immune Network Pub Date : 2024-12-19 eCollection Date: 2024-12-01 DOI: 10.4110/in.2024.24.e42

Daniel Beckers, Ashwin K Jainarayanan, Michael L Dustin, Jesusa Capera

{"title":"T Cell Resistance: On the Mechanisms of T Cell Non-activation.","authors":"Daniel Beckers, Ashwin K Jainarayanan, Michael L Dustin, Jesusa Capera","doi":"10.4110/in.2024.24.e42","DOIUrl":"10.4110/in.2024.24.e42","url":null,"abstract":"Immunological tolerance is a fundamental arm of any functioning immune system. Not only does tolerance mitigate collateral damage from host immune responses, but in doing so permits a robust response sufficient to clear infection as necessary. Yet, despite occupying such a cornerstone, research aiming to unravel the intricacies of tolerance induction is mired by interchangeable and often misused terminologies, with markers and mechanistic pathways that beg the question of redundancy. In this review we aim to define these boarders by providing new perspectives to long-standing theories of tolerance. Given the central role of T cells in enforcing immune cascades, in this review we choose to explore immunological tolerance through the perspective of T cell 'resistance to activation,' to delineate the contexts in which one tolerance mechanism has evolved over the other. By clarifying the important biological markers and cellular players underpinning T cell resistance to activation, we aim to encourage more purposeful and directed research into tolerance and, more-over, potential therapeutic strategies in autoimmune diseases and cancer. The tolerance field is in much need of reclassification and consideration, and in this review, we hope to open that conversation.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 6","pages":"e42"},"PeriodicalIF":4.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bifidobacterium longum RAPO Attenuates Dermal and Pulmonary Fibrosis in a Mouse Model of Systemic Sclerosis through Macrophage Modulation and Growth of Short-Chain Fatty Acid Producers. 长双歧杆菌RAPO通过巨噬细胞调节和短链脂肪酸产生物的生长，减轻系统性硬化症小鼠模型的皮肤和肺纤维化。

IF 4.3 4区医学

Immune Network Pub Date : 2024-12-17 eCollection Date: 2024-12-01 DOI: 10.4110/in.2024.24.e41

Hee Jin Park, Dakyum Yu, Seong-Tshool Hong, Juyeon Lee, Sang-Jun Park, Myeong Soo Park, Hanna Lee, Mingyo Kim, Yun-Hong Cheon, Seung-Geun Lee, Dong Hyun Sohn, Jae-Bum Jun, Suhee Kim, Sang-Il Lee

{"title":"Bifidobacterium longum RAPO Attenuates Dermal and Pulmonary Fibrosis in a Mouse Model of Systemic Sclerosis through Macrophage Modulation and Growth of Short-Chain Fatty Acid Producers.","authors":"Hee Jin Park, Dakyum Yu, Seong-Tshool Hong, Juyeon Lee, Sang-Jun Park, Myeong Soo Park, Hanna Lee, Mingyo Kim, Yun-Hong Cheon, Seung-Geun Lee, Dong Hyun Sohn, Jae-Bum Jun, Suhee Kim, Sang-Il Lee","doi":"10.4110/in.2024.24.e41","DOIUrl":"10.4110/in.2024.24.e41","url":null,"abstract":"Systemic sclerosis (SSc) is a complex autoimmune disease with an unclear etiology and no effective treatments. Recent research has suggested involvement of the microbiome in SSc pathogenesis. This study aimed to identify specific microbial species associated with SSc and explore their therapeutic potential. Serum Abs against 384 intestinal microbial species revealed a significant depletion in Abs against Bifidobacterium longum in patients with SSc compared to healthy controls. In a bleomycin-induced SSc mouse model, oral administration of B. longum strain RAPO attenuated skin and lung fibrosis, accompanied by reduced infiltration of inflammatory monocytes/macrophages and downregulation of pro-inflammatory cytokines and chemoattractant Ccl2 genes in lymph nodes and fibrotic tissues. B. longum RAPO treatment restored fecal microbial diversity and augmented short-chain fatty acid (SCFA)-producing bacteria in the gut, leading to increased fecal butyrate levels and upregulated SCFA receptor Gpr41 in the mesenteric lymph node. In vitro, B. longum RAPO and its culture supernatant suppressed the expressions of pro-inflammatory cytokine genes in macrophages and inhibited myofibroblast differentiation in fibroblasts. These findings highlight the probiotic potential of B. longum RAPO in preventing tissue fibrosis by modulating macrophage activity and promoting the growth of SCFA-producing bacteria, underscoring the therapeutic potential of microbial modulation in SSc.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 6","pages":"e41"},"PeriodicalIF":4.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beyond Tumor Borders: Intratumoral Microbiome Effects on Tumor Behavior and Therapeutic Responses. 超越肿瘤边界：肿瘤内微生物组对肿瘤行为和治疗反应的影响。

IF 4.3 4区医学

Immune Network Pub Date : 2024-12-09 eCollection Date: 2024-12-01 DOI: 10.4110/in.2024.24.e40

Zakia Harmak, Abdou-Samad Kone, Amina Ghouzlani, Bouchra Ghazi, Abdallah Badou

{"title":"Beyond Tumor Borders: Intratumoral Microbiome Effects on Tumor Behavior and Therapeutic Responses.","authors":"Zakia Harmak, Abdou-Samad Kone, Amina Ghouzlani, Bouchra Ghazi, Abdallah Badou","doi":"10.4110/in.2024.24.e40","DOIUrl":"10.4110/in.2024.24.e40","url":null,"abstract":"The human body contains a diverse array of microorganisms, which exert a significant impact on various physiological processes, including immunity, and can significantly influence susceptibility to various diseases such as cancer. Recent advancements in metagenomic sequencing have uncovered the role of intratumoral microbiome, which covertly altered the development of cancer, the growth of tumors, and the response to existing treatments through multiple mechanisms. These mechanisms involve mainly DNA damage induction, oncogenic signaling pathway activation, and the host's immune response modulation. To explore novel therapeutic options and effectively target and regulate the intratumoral microbiome, a comprehensive understanding of these processes is indispensable. Here, we will explore various potential actions of the intratumoral microbiome concerning the initiation and progression of tumors. We will examine its impact on responses to chemotherapy, radiotherapy, and immunotherapy. Additionally, we will discuss the current state of knowledge regarding the use of genetically modified bacteria as a promising treatment option for cancer.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 6","pages":"e40"},"PeriodicalIF":4.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simultaneous Epigenetic and Gene Expression Profiling at Single Cell Resolution Uncovers Stem-Like Treg Subsets Induced With Oligonucleotide Expansion in Humans. 在单细胞分辨率下同时进行表观遗传和基因表达谱分析，揭示了人类中由寡核苷酸扩增诱导的茎样Treg亚群。

IF 4.3 4区医学

Immune Network Pub Date : 2024-10-24 eCollection Date: 2024-12-01 DOI: 10.4110/in.2024.24.e39

Hyo Jeong Nam, Jeong-Ryeol Gong, Yong-Hee Kim, Thuy Nguyen-Phuong, Nari Byun, Jeong Heon Yoon, Yong Chan Kim, Hyunwoo Chung, Brian Hyohyoung Lee, Haeyoon Kwon, Woochan Lee, Sung-Jun Kang, Kyunghyuk Park, Bukyoung Cha, Jong-Il Kim, Hyun Je Kim

{"title":"Simultaneous Epigenetic and Gene Expression Profiling at Single Cell Resolution Uncovers Stem-Like Treg Subsets Induced With Oligonucleotide Expansion in Humans.","authors":"Hyo Jeong Nam, Jeong-Ryeol Gong, Yong-Hee Kim, Thuy Nguyen-Phuong, Nari Byun, Jeong Heon Yoon, Yong Chan Kim, Hyunwoo Chung, Brian Hyohyoung Lee, Haeyoon Kwon, Woochan Lee, Sung-Jun Kang, Kyunghyuk Park, Bukyoung Cha, Jong-Il Kim, Hyun Je Kim","doi":"10.4110/in.2024.24.e39","DOIUrl":"10.4110/in.2024.24.e39","url":null,"abstract":"Tregs play a central role in maintaining immune tolerance. Recent progress in the clinical application of Tregs underscores their potential for cell therapy. Nevertheless, a notable hurdle remains in producing functional Tregs in vitro. There is also a lack of detailed studies evaluating the function of Tregs during their ex vivo expansion process. Our prior investigation showed that the ex vivo expansion with oligonucleotides produces FoxP3highHelioshigh subsets. To investigate how oligonucleotides in culture media influence on gene expression and epigenetic states at single cell resolution, we sorted Tregs from healthy individuals and profiled in vitro oligonucleotide-expanded and non-expanded Tregs. We discovered a subset of Tregs, specifically enriched in expanded Tregs (seTregs), through oligonucleotide-induced expansion. seTregs showed an enhancement in both stem-like characteristics and functional attributes. Through analysis of histone modification data and gene regulatory networks, we elucidated IKZF2 (Helios) as a pivotal transcription factor in generating these cell subsets. We believe these findings offer insights into evaluating functional regulation of in vitro expanded Tregs aimed at manufacturing Treg-based cell therapies.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 6","pages":"e39"},"PeriodicalIF":4.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of Inflammasome-Associated Innate Immune Receptors in Cancer. 炎症体相关先天性免疫受体在癌症中的作用

IF 4.3 4区医学

Immune Network Pub Date : 2024-10-21 eCollection Date: 2024-10-01 DOI: 10.4110/in.2024.24.e38

Ruby E Dawson, Brendan J Jenkins

{"title":"The Role of Inflammasome-Associated Innate Immune Receptors in Cancer.","authors":"Ruby E Dawson, Brendan J Jenkins","doi":"10.4110/in.2024.24.e38","DOIUrl":"https://doi.org/10.4110/in.2024.24.e38","url":null,"abstract":"Dysregulated activation of the innate immune system is a critical driver of chronic inflammation that is associated with at least 30% of all cancers. Innate immunity can also exert tumour-promoting effects (e.g. proliferation) directly on cancer cells in an intrinsic manner. Conversely, innate immunity can influence adaptive immunity-based anti-tumour immune responses via Ag-presenting dendritic cells that activate natural killer and cytotoxic T cells to eradicate tumours. While adaptive anti-tumour immunity has underpinned immunotherapy approaches with immune checkpoint inhibitors and chimeric Ag receptor-T cells, the clinical utility of innate immunity in cancer is underexplored. Innate immune responses are governed by pattern recognition receptors, which comprise several families, including Toll-like, nucleotide-binding oligomerization domain-containing (NOD)-like and absent-in-melanoma 2 (AIM2)-like receptors. Notably, a subset of NOD-like and AIM2-like receptors can form large multiprotein \"inflammasome\" complexes which control maturation of biologically active IL-1β and IL-18 cytokines. Over the last decade, it has emerged that inflammasomes can coordinate contrasting pro- and anti-tumour responses in cancer and non-cancer (e.g. immune, stromal) cells. Considering the importance of inflammasomes to the net output of innate immune responses, here we provide an overview and discuss recent advancements on the diverse role of inflammasomes in cancer that have underpinned their potential targeting in diverse malignancies.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 5","pages":"e38"},"PeriodicalIF":4.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STING-STAT6 Signaling Pathway Promotes IL-4⁺ and IFN-α⁺ Fibrotic T Cell Activation and Exacerbates Scleroderma in SKG Mice. STING-STAT6信号通路促进IL-4+和IFN-α+纤维化T细胞活化并加重SKG小鼠的硬皮病。

IF 4.3 4区医学

Immune Network Pub Date : 2024-10-16 eCollection Date: 2024-10-01 DOI: 10.4110/in.2024.24.e37

Kun Hee Lee, Jin Seok Woo, Ha Yeon Jeong, Jeong Won Choi, Chul Hwan Bang, Jeehee Youn, Sung-Hwan Park, Mi-La Cho

{"title":"STING-STAT6 Signaling Pathway Promotes IL-4+ and IFN-α+ Fibrotic T Cell Activation and Exacerbates Scleroderma in SKG Mice.","authors":"Kun Hee Lee, Jin Seok Woo, Ha Yeon Jeong, Jeong Won Choi, Chul Hwan Bang, Jeehee Youn, Sung-Hwan Park, Mi-La Cho","doi":"10.4110/in.2024.24.e37","DOIUrl":"https://doi.org/10.4110/in.2024.24.e37","url":null,"abstract":"Systemic sclerosis (SS) is an autoimmune disease and pathological mechanisms of SS are unclear. In this study, we investigated the role of T cells in the progression of SS using SKG mice and humanized mice. SKG mice have a spontaneous point mutation in ZAP70. We induced scleroderma in SKG mice and a humanized SS mouse model to assess whether T cell-mediated immune responses induce SS. As a result, we found increased dermal thickness, fibrosis, and lymphocyte infiltration in skin tissue in SKG SS mice compared to BALB/c mice (control). Also, blood cytokine level, including IL-4- and IFN-α which are produced by CD4+ T cells via STIM1/STING/STAT6/IRF3 signaling pathways, were increased in SKG mice. Interestingly, skin fibrosis was reduced by inhibiting STING pathway in skin fibroblast. Next, we demonstrated the pathophysiological role of IL-4 and IFN-α in skin fibrosis using a humanized SS mouse model and found increased IL-4- and IFN-α-producing CD4+ T cells and fibrosis. In this study, we found that STING-induced production of IL-4- and type I IFN by CD4+ T cells is a key factor in mouse model and humanized mouse model of SS. Our findings suggest that the STING/STAT6/IRF3 signaling pathways are potential therapeutic targets in SS.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 5","pages":"e37"},"PeriodicalIF":4.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increased Inflammatory Responses in Patients With Active Disseminated Non-Tuberculous Mycobacterial Infection and High Anti-Interferon-Gamma Autoantibodies. 活动性播散性非结核分枝杆菌感染和高抗干扰素-γ自身抗体患者的炎症反应增强

IF 4.3 4区医学

Immune Network Pub Date : 2024-10-08 eCollection Date: 2024-10-01 DOI: 10.4110/in.2024.24.e36

Pattaraporn Srisai, Chanchai Hongsa, Yothin Hinwan, Varis Manbenmad, Ploenchan Chetchotisakd, Siriluck Anunnatsiri, Kiatichai Faksri, Todsapol Techo, Kanin Salao, Steven W Edwards, Arnone Nithichanon

{"title":"Increased Inflammatory Responses in Patients With Active Disseminated Non-Tuberculous Mycobacterial Infection and High Anti-Interferon-Gamma Autoantibodies.","authors":"Pattaraporn Srisai, Chanchai Hongsa, Yothin Hinwan, Varis Manbenmad, Ploenchan Chetchotisakd, Siriluck Anunnatsiri, Kiatichai Faksri, Todsapol Techo, Kanin Salao, Steven W Edwards, Arnone Nithichanon","doi":"10.4110/in.2024.24.e36","DOIUrl":"https://doi.org/10.4110/in.2024.24.e36","url":null,"abstract":"Adult-onset immunodeficiency (AOID) is associated with the presence of anti-IFN-γ autoantibodies (auAbs). In disseminated nontuberculous mycobacterial (dNTM) infection with AOID, neutralization of IFN-γ by auAb may play a role in disease susceptibility, but other molecular mechanisms are likely to contribute. In this study, dNTM patients, including inactive, active but non-progressive and active, progressive cases were enrolled to measure plasma anti-IFN-γ auAb by ELISA and underwent whole-blood RNA sequencing. Healthy control individuals were also enrolled. Plasma IL-8 was then quantified to confirm transcriptomic analysis. Results revealed that anti-IFN-γ auAb titers were significantly increased in patients with active stage of disease. Gene expression could separate patients with active infection from individuals with no signs of infection (inactive patients and healthy controls). In active cases, there was over-expression of inflammatory pathways and under-expression of type-2 immunity pathways. Interestingly, increased levels of plasma IL-8 (p=0.0167) not only confirmed gene expression results but also correlated with the presence of neutrophilic dermatitis (p=0.0244). In conclusion, our findings highlight the value of anti-IFN-γ auAb titers for predicting disease reactivity and first propose IL-8 as a promising mediator to be further explored, given its correlation with skin reactive disease, a hallmark of active dNTM infection.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 5","pages":"e36"},"PeriodicalIF":4.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0