Immune Network最新文献

Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease. 补体过敏毒素信号在健康和疾病中的神秘作用。

IF 4.1 4区医学

Immune Network Pub Date : 2025-08-20 eCollection Date: 2025-08-01 DOI: 10.4110/in.2025.25.e32

Anthony Shadid, Kathryn D Hok, Aleksey Y Domozhirov, Tingting Weng-Mills, Marie-Françoise Doursout, Nirmal K Banda, Marcos I Restrepo, Pooja Shivshankar

{"title":"Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.","authors":"Anthony Shadid, Kathryn D Hok, Aleksey Y Domozhirov, Tingting Weng-Mills, Marie-Françoise Doursout, Nirmal K Banda, Marcos I Restrepo, Pooja Shivshankar","doi":"10.4110/in.2025.25.e32","DOIUrl":"10.4110/in.2025.25.e32","url":null,"abstract":"Complement anaphylatoxins C3a and C5a are potent immunomodulators whose impact extends well beyond their traditional roles in innate immunity. Acting through G protein-coupled receptors C3aR, C5aR1, and C5aR2, these peptides take part in coordinating immune cell recruitment, vascular tone, and tissue remodeling. Yet their functions are deeply context-dependent: while they play essential roles in microbial clearance and immune coordination, their overactivation contributes to immunopathology in a wide range of diseases. The anaphylatoxins play key roles in early pathogen containment but can also drive cytokine storm and tissue damage, as in coronavirus disease 2019 (COVID-19) and bacterial sepsis. In autoimmune conditions, the anaphylatoxins promote leukocyte infiltration and complement-mediated tissue injury. In chronic diseases, they contribute to fibrosis in diabetic kidney disease and idiopathic pulmonary fibrosis, and anaphylatoxins disrupt neurovascular integrity in neurodegenerative diseases. In cancer, C3a and C5a shape the tumor microenvironment by facilitating immune evasion, angiogenesis, and metastasis. As complement-targeted therapies gain momentum in clinical settings-particularly in the treatment of genetic disorders, such as paroxysmal nocturnal hemoglobinuria, more recently COVID-19, and cancer-a deeper mechanistic understanding of C3a and C5a signaling is imperative as we advance closer toward precision medicine, and this review aims to inform future approaches for therapeutic complement modulation.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 4","pages":"e32"},"PeriodicalIF":4.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015024","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

Does the Single Nucleotide Polymorphism rs2228145 in IL6R Truly Reflect IL-6 Signaling in Mendelian Randomization Studies? 孟德尔随机化研究中il - 6r单核苷酸多态性rs2228145是否真实反映IL-6信号？

IF 4.1 4区医学

Immune Network Pub Date : 2025-08-18 eCollection Date: 2025-08-01 DOI: 10.4110/in.2025.25.e31

Mengyi Zhu, Minghui Cao, Liling Lin

引用次数: 0

Arginine Metabolism in Cancer Biology and Immunotherapy. 精氨酸代谢在肿瘤生物学和免疫治疗中的应用。

IF 4.1 4区医学

Immune Network Pub Date : 2025-08-12 eCollection Date: 2025-08-01 DOI: 10.4110/in.2025.25.e30

DingYuan Bai, YuXuan Zhou, LingJie Jing, Cheng Guo, QuanJun Yang

引用次数: 0

Adoptive Cellular Therapies in Pediatric Leukemia Patients After Allogeneic-Hematopoietic Stem Cell Transplants. 异基因造血干细胞移植后儿童白血病患者的过继细胞治疗。

IF 4.1 4区医学

Immune Network Pub Date : 2025-08-12 eCollection Date: 2025-08-01 DOI: 10.4110/in.2025.25.e29

Leanne Palichuk, Enoch Tin, Jongbok Lee

{"title":"Adoptive Cellular Therapies in Pediatric Leukemia Patients After Allogeneic-Hematopoietic Stem Cell Transplants.","authors":"Leanne Palichuk, Enoch Tin, Jongbok Lee","doi":"10.4110/in.2025.25.e29","DOIUrl":"10.4110/in.2025.25.e29","url":null,"abstract":"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides a curative potential for high-risk patients with leukemia following first-line therapies, driven by potent immune cell-dependent anti-tumour activities. Although deep remission can be achieved, many patients relapse after allo-HSCT, and further treatment options are scarce. Given the potent immune cell-mediated anti-leukemic effects of allo-HSCT, adoptive cellular therapies (ACTs) have been explored as an adjunctive therapy to enhance the efficacy of allo-HSCT or to treat patients who relapse after allo-HSCT. Interestingly, evidence suggests a stratified therapeutic approach is warranted between pediatric and adult leukemic cases, due to differences in genetic mutations and treatment tolerability. However, pediatric-specific investigations are limited, especially in the cellular therapeutic landscape to treat relapse after allo-HSCT. Known severe toxicities attributed to ACTs need to be addressed for this younger population to ensure prolonged quality of life. This review summarizes the current landscape of ACTs, including donor lymphocyte infusion, chimeric Ag receptor-T cell, NK cell, and double-negative T cell therapies, for treating pediatric leukemia post allo-HSCT, highlighting efficacy, safety, and gaps in pediatric-specific data to guide future research.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 4","pages":"e29"},"PeriodicalIF":4.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015056","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

Distinct T Cell Dysregulation Reflects Disease Severity and Progression in Infantile Epileptic Spasms Syndrome and Lennox-Gastaut Syndrome. 不同的T细胞失调反映了婴儿癫痫痉挛综合征和lenox -胃痉挛综合征的疾病严重程度和进展。

IF 4.1 4区医学

Immune Network Pub Date : 2025-08-11 eCollection Date: 2025-08-01 DOI: 10.4110/in.2025.25.e28

Leechung Chang, Yeo-Jin Jeong, Haeun Chang, Hyeon Deok Sang, Ki-Nam Kwon, Su-Bin Lee, Si-Yoon Kim, You Min Kang, Sungji Ha, Se Hee Kim, Keun-Ah Cheon, Ho-Keun Kwon

{"title":"Distinct T Cell Dysregulation Reflects Disease Severity and Progression in Infantile Epileptic Spasms Syndrome and Lennox-Gastaut Syndrome.","authors":"Leechung Chang, Yeo-Jin Jeong, Haeun Chang, Hyeon Deok Sang, Ki-Nam Kwon, Su-Bin Lee, Si-Yoon Kim, You Min Kang, Sungji Ha, Se Hee Kim, Keun-Ah Cheon, Ho-Keun Kwon","doi":"10.4110/in.2025.25.e28","DOIUrl":"10.4110/in.2025.25.e28","url":null,"abstract":"Developmental and epileptic encephalopathies (DEEs), including Infantile Epileptic Spasms Syndrome (IESS) and Lennox-Gastaut Syndrome (LGS), are severe pediatric conditions characterized by profound developmental delays and treatment-resistant epilepsy. Although steroid therapies provide some clinical benefits, the underlying immunological mechanisms remain poorly understood. In this study, we performed comprehensive immune profiling using multi-parametric flow cytometry on PBMCs from IESS (n=25) and LGS (n=9) patients, comparing them with age-matched healthy controls (n=54). Our findings identified distinct patterns of immune dysregulation: IESS patients exhibited reduced naïve CD4+ T cells, an altered CD4/CD8 ratio, and diminished TNFα production in CD4+ T cells. Conversely, LGS patients demonstrated an increase in central memory CD4+ T cells, marked dysfunction of Tregs, and heightened activation of CD8+ T cells. Notably, elevated activated CD8+ T cells in IESS patients correlated significantly with clinical severity and demonstrated enhanced responsiveness to viral peptides, suggesting prior viral infections may exacerbate disease progression. Collectively, our findings demonstrate distinct immune signatures associated with disease severity and progression in DEE, suggesting their potential utility as biomarkers. Further studies are necessary to determine whether targeting these immune pathways could provide clinical benefits.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 4","pages":"e28"},"PeriodicalIF":4.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015027","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

A Novel Approach of T Cell Receptor Classification Reveals Dynamic Interactions Amongst Diet, Microbiota, and Host T Cells. 一种新的T细胞受体分类方法揭示了饮食、微生物群和宿主T细胞之间的动态相互作用。

IF 4.1 4区医学

Immune Network Pub Date : 2025-08-07 eCollection Date: 2025-08-01 DOI: 10.4110/in.2025.25.e27

Jisun Jung, Jaeu Yi

引用次数: 0

Pediatric Atopic Dermatitis Exhibits Distinctive Patterns in JAK/STAT Pathway Activation and CD6-ALCAM Signaling. 儿童特应性皮炎在JAK/STAT通路激活和CD6-ALCAM信号传导中表现出独特的模式。

IF 4.1 4区医学

Immune Network Pub Date : 2025-06-20 eCollection Date: 2025-08-01 DOI: 10.4110/in.2025.25.e26

Soyoung Jeong, Sanghee Shin, Hyun Seung Choi, So-Jung Choi, Sehun Jang, Jeongmin Song, Ji Su Lee, Dong Hun Lee, Hyun Je Kim, Jihyun Kim, Kangmo Ahn

{"title":"Pediatric Atopic Dermatitis Exhibits Distinctive Patterns in JAK/STAT Pathway Activation and CD6-ALCAM Signaling.","authors":"Soyoung Jeong, Sanghee Shin, Hyun Seung Choi, So-Jung Choi, Sehun Jang, Jeongmin Song, Ji Su Lee, Dong Hun Lee, Hyun Je Kim, Jihyun Kim, Kangmo Ahn","doi":"10.4110/in.2025.25.e26","DOIUrl":"10.4110/in.2025.25.e26","url":null,"abstract":"Pediatric atopic dermatitis (AD) shows distinct clinical characteristics compared to adult AD, suggesting unique inflammatory profiles that may influence disease prognosis and treatment response. We aimed to identify unique immune signatures of pediatric AD and investigate the differences between pediatric and adult AD patients. Nine pediatric (6-16 years) and 12 adult (20-60 years) were enrolled. PBMCs were collected from AD patients and age- and sex-matched healthy controls (HCs). Transcriptomic profiles were analyzed using single-cell RNA sequencing, and the immune phenotypes of adult and pediatric AD were compared. Th2 gene expression was elevated in both adult and pediatric AD, while Th1, Th17, and Th22 gene expression was downregulated in pediatric AD but not in adults. Genes involved in JAK/STAT signaling pathway, which were upregulated in adult AD, were not significantly increased in pediatric AD. The CD6-activated leukocyte cell adhesion molecule (ALCAM) pathway was upregulated in pediatric AD compared to pediatric HCs, but not in adult AD. Pediatric AD reveals distinct immune signatures, including a lack of JAK/STAT pathway upregulation observed in adult AD and a unique activation of the CD6-ALCAM pathway. These findings highlight the importance of age-specific treatment strategies in AD patients.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 4","pages":"e26"},"PeriodicalIF":4.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015072","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

Soluble CCR2-Expressing Mesenchymal Stem Cells Inhibit Osteoarthritis Development and Progression. 可溶性表达ccr2的间充质干细胞抑制骨关节炎的发生和进展

IF 4.3 4区医学

Immune Network Pub Date : 2025-06-16 eCollection Date: 2025-06-01 DOI: 10.4110/in.2025.25.e24

Hyun Sik Na, Seon-Young Lee, Dong Hwan Lee, Keun-Hyung Cho, Seon Ae Kim, Eun Jeong Go, A Ram Lee, Jeong Su Lee, Yeon Su Lee, In Gyu Um, Se Gyeong Han, Mi-La Cho, Seok Jung Kim

{"title":"Soluble CCR2-Expressing Mesenchymal Stem Cells Inhibit Osteoarthritis Development and Progression.","authors":"Hyun Sik Na, Seon-Young Lee, Dong Hwan Lee, Keun-Hyung Cho, Seon Ae Kim, Eun Jeong Go, A Ram Lee, Jeong Su Lee, Yeon Su Lee, In Gyu Um, Se Gyeong Han, Mi-La Cho, Seok Jung Kim","doi":"10.4110/in.2025.25.e24","DOIUrl":"10.4110/in.2025.25.e24","url":null,"abstract":"Many studies of osteoarthritis (OA) have focused on the use of pain-suppressing drugs and stem cell treatments for cartilage repair. In a previous study, we reported the therapeutic effect of soluble C-C chemokine receptor type 2 (sCCR2) gene therapy on OA. Here, we aimed to demonstrate that sCCR2-expressing stem cells exhibits superior efficacy compared to mesenchymal stem cell (MSC) alone. We used monosodium iodoacetate to induce OA in a Wistar rat model for our experiments. Soluble form of CCR2 was transfected into chondrocytes. We analyzed both in vitro and in vivo systems using sCCR2 E3-transfected MSCs (sCEMs). MCP-1 reduced chondrogenesis, whereas sCEMs improved it. Additionally, disease development was suppressed in MCP-1 conditional knockout mice. In the OA rat model, injection of sCEMs showed significant effects with respect to pain control and reduction of joint cartilage inflammation and damage compared with injection of MOCK-MSCs. These findings indicate that sCEMs inhibit MCP-1, reducing pain and OA-induced cartilage damage and inducing chondroprotection. Inhibiting MCP-1/CCR2 signaling has a significant therapeutic effect on OA. Therefore, sCEM may be an effective treatment for OA.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 3","pages":"e24"},"PeriodicalIF":4.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575394","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

Pathotype-Specific Expression of Granzyme-Perforin Pathway Genes and Their Association With Clinical Disease Activity in Early Rheumatoid Arthritis and in a Randomized Clinical Trial. 颗粒酶-穿孔素途径基因在早期类风湿关节炎的病理型特异性表达及其与临床疾病活动性的关联及一项随机临床试验

IF 4.1 4区医学

Immune Network Pub Date : 2025-06-16 eCollection Date: 2025-08-01 DOI: 10.4110/in.2025.25.e25

Francisco G La Rosa, Larry W Moreland, Luigi Nibali, Mike Curtis, Kevin D Deane, Colin Strickland, Jennifer Seifert, Carson Keeter, Dmitri Simberg, Robert I Scheinman, Rachel Lau, Costantino Pitzalis, Myles J Lewis, V Michael Holers, Nirmal K Banda

{"title":"Pathotype-Specific Expression of Granzyme-Perforin Pathway Genes and Their Association With Clinical Disease Activity in Early Rheumatoid Arthritis and in a Randomized Clinical Trial.","authors":"Francisco G La Rosa, Larry W Moreland, Luigi Nibali, Mike Curtis, Kevin D Deane, Colin Strickland, Jennifer Seifert, Carson Keeter, Dmitri Simberg, Robert I Scheinman, Rachel Lau, Costantino Pitzalis, Myles J Lewis, V Michael Holers, Nirmal K Banda","doi":"10.4110/in.2025.25.e25","DOIUrl":"10.4110/in.2025.25.e25","url":null,"abstract":"Rheumatoid arthritis (RA) is an autoimmune disease. We examined gene expression of five granzymes (GZMs), perforin (PRF-1), and serglycin (SRGN) from tissues derived from pathobiology of early arthritis cohort (PEAC) and phase 4 randomized controlled trial in anti-TNF inadequate responder patients with RA (R4RA). Information regarding gene expression of GZMs, PRF-1, and SRGN in synovium and blood pathotypes and their correlations with disease activity scores with 28 joints (DAS28)-erythrocyte sedimentation rate and with DAS28-C-reactive protein in early RA (eRA) is lacking. To determine the expression of these genes in synovium and blood pathotypes, we analyzed bulk RNA-sequencing data. The percentage of CD8+ T cells was determined in synovium, and the presence of Porphyromonas gingivalis was examined in synovium. The expression of GZM A, B, H, K, M, PRF-1, and SRGN was significantly higher in the lymphoid pathotype in the PEAC and R4RA synovium. The percentage of CD8 T cells was low, and minor speckles (Ag-reactivity) of P. gingivalis Ag were detected in eRA synovium. Rituximab and tocilizumab treatment in R4RA decreased the expression of all GZMs, PRF-1, and SRGN in the synovium. In conclusion, components of the GZM-PRF-1 pathway are upregulated in RA and may play a mechanistic role.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 4","pages":"e25"},"PeriodicalIF":4.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015014","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

Nanobody-Based CAR NK Cells for Possible Immunotherapy of Mesothelin⁺ Tumors. 纳米体CAR - NK细胞可能用于间皮素+肿瘤的免疫治疗。

IF 4.3 4区医学

Immune Network Pub Date : 2025-06-13 eCollection Date: 2025-06-01 DOI: 10.4110/in.2025.25.e23

Dana Jung, Eunjeong Choi, Young-Hee Jeoung, Juheon Lee, Eun-Yeung Gong, Seo-Gyeong Jo, Kyunghee Noh, Kyungsoo Ha, Gabbine Wee, Hyeran Kim, Juyeon Jung, Seokho Kim

{"title":"Nanobody-Based CAR NK Cells for Possible Immunotherapy of Mesothelin+ Tumors.","authors":"Dana Jung, Eunjeong Choi, Young-Hee Jeoung, Juheon Lee, Eun-Yeung Gong, Seo-Gyeong Jo, Kyunghee Noh, Kyungsoo Ha, Gabbine Wee, Hyeran Kim, Juyeon Jung, Seokho Kim","doi":"10.4110/in.2025.25.e23","DOIUrl":"10.4110/in.2025.25.e23","url":null,"abstract":"Chimeric Ag receptor (CAR)-engineered immune cells have demonstrated remarkable clinical efficacy, particularly in hematologic malignancies. Central to their success is the Ag-binding domain of the CAR, which governs both target specificity and therapeutic efficacy. Nanobodies (Nbs) possess a single-domain architecture and smaller molecular size, making them particularly amenable to the construction of tandem CARs that can co-target multiple Ags. This structural flexibility is advantageous for addressing tumor heterogeneity and reducing the risk of Ag escape in solid malignancies. Here, we developed mesothelin (MSLN)-specific nanobody-based chimeric Ag receptor-NK (Nb CAR-NK) cells using a synthetic nanobody identified from a phage display VHH library. The nanobody was selected after three rounds of biopanning and validated for high affinity and specificity using surface plasmon resonance and flow cytometry. The selected nanobody-based chimeric Ag receptor (Nb-CAR) construct was introduced into ex vivo expanded umbilical cord blood-derived NK cells via third-generation lentiviral transduction, resulting in stable expression and functional CAR-NK cells. The Nb CAR-NK cells exhibited potent cytotoxicity against MSLN-positive pancreatic cancer cells in vitro and significantly suppressed tumor growth in xenograft models. These findings support the clinical potential of Nb CAR-NK cells and highlight the value of Nb-CAR designs for targeting cell-surface Ags in solid tumors.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"25 3","pages":"e23"},"PeriodicalIF":4.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575392","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