Genes and immunity最新文献_第3页

Longitudinal omics reveals immune repertoire remodeling in myasthenia gravis patients post-tacrolimus therapy 纵向组学揭示重症肌无力患者在他克莫司治疗后的免疫系统重构。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-03-30 DOI: 10.1038/s41435-026-00395-1

Ting He, Liu Wang, Kangzhi Chen, Qian Zhou, Liqun Xu, Zhaohui Luo, Huan Yang

{"title":"Longitudinal omics reveals immune repertoire remodeling in myasthenia gravis patients post-tacrolimus therapy","authors":"Ting He, Liu Wang, Kangzhi Chen, Qian Zhou, Liqun Xu, Zhaohui Luo, Huan Yang","doi":"10.1038/s41435-026-00395-1","DOIUrl":"10.1038/s41435-026-00395-1","url":null,"abstract":"Myasthenia gravis (MG) is a T/B cell-driven autoimmune disease. The immunomodulatory mechanisms of the common immunosuppressant tacrolimus (TAC) on the immune repertoire are unclear. This study investigated TAC’s immunomodulatory effects via high-throughput sequencing of peripheral blood mononuclear cells from four MG patients pre- and post-four months of TAC monotherapy, revealing dynamic T-cell receptor (TCR) and B-cell receptor (BCR) repertoire remodeling. The immune repertoire of MG patients was characterized by a skewed usage of TRBV gene families compared to healthy controls, indicating an underlying immune dysfunction. Longitudinal analysis post-TAC therapy revealed potential downregulation of IGHV1-69 and IGHV3-43 gene frequencies (p < 0.05, FDR > 0.1), alongside non-significant trends toward shorter CDR3 lengths and reduced clonal diversity in both IGH and TRB (p > 0.05). The BCR repertoire underwent greater dynamic remodeling, while the TCR repertoire remained relatively stable, as evidenced by the persistence of dominant clones and overlapping TRB clones. BCR diversity and V or J gene usage in TCR and BCR showed potential associations with clinical severity. These data reveal skewed antigen recognition profiles in MG pathogenesis, with TAC orchestrating multimodal immunomodulation through peripheral immune repertoire reshaping.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"401-409"},"PeriodicalIF":4.2,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581022","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

Trub1-mediated pseudouridylation is dispensable for immune cell development and homeostasis trub1介导的假尿嘧啶化对于免疫细胞的发育和体内平衡是必不可少的。

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-03-24 DOI: 10.1038/s41435-026-00393-3

Vanshika Malviya, Cuong Thi Pham, Lauren Michiels, Laura Seldeslachts, Virginie Marchand, Gerlanda Vella, Laurie Rangan, Yuri Motorin, Greetje Vande Velde, Pierre Lemaitre, Susan M. Schlenner

{"title":"Trub1-mediated pseudouridylation is dispensable for immune cell development and homeostasis","authors":"Vanshika Malviya, Cuong Thi Pham, Lauren Michiels, Laura Seldeslachts, Virginie Marchand, Gerlanda Vella, Laurie Rangan, Yuri Motorin, Greetje Vande Velde, Pierre Lemaitre, Susan M. Schlenner","doi":"10.1038/s41435-026-00393-3","DOIUrl":"10.1038/s41435-026-00393-3","url":null,"abstract":"Epitranscriptomic modifications are evolutionarily conserved changes to RNA and are present in all RNA types, including mRNA. Next to methylation, pseudouridine is also a prevalent modification found in mRNA and other RNA types. Pseudouridylation of RNA improves RNA stability, RNA stacking and translation fidelity. While m6A RNA methylation has been demonstrated to regulate the activation of various immune cell types, such as T cells, dendritic cells or NK cells, insight into the role of pseudouridine in the immune system is limited. Trub1 is one of 13 pseudouridine synthases (PUS) and has been suggested to co-install the majority of pseudouridine residues on mRNA alongside the activity of PUS7 and has been reported to install pseudouridine in tRNA. Against this background, we hypothesized that Trub1 may regulate immune cell development, homeostasis or functional differentiation. Using conditional and global Trub1-deficient mice, in vivo competition in mixed bone marrow chimaeras and high-parametric flow cytometry, we interrogated the role of Trub1 in T cells, B cells, NK cells and myeloid cells. Despite our rigorous analyses and the identification of Trub1-dependent pseudouridine residues in mitochondrial tRNAs, we did not identify a significant role for Trub1-mediated pseudouridylation in immune cells at steady state or during disease. We hence reason that the role of Trub1 in mRNA pseudouridylation has previously been overestimated in computational studies or that co-installations of pseudouridine at other positions in the same RNA molecules may compensate for the lack of Trub1-installed modifications.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 3","pages":"363-373"},"PeriodicalIF":4.5,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41435-026-00393-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Heparin inhibits NLRP3-dependent pyroptosis in acute pancreatitis 肝素抑制急性胰腺炎nlrp3依赖性焦亡。

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-03-19 DOI: 10.1038/s41435-026-00390-6

Guanxiu Tang, Wangjun Yan, Xulin Li, Xuan Zhang, Di Wu, Shangping Zhao

{"title":"Heparin inhibits NLRP3-dependent pyroptosis in acute pancreatitis","authors":"Guanxiu Tang, Wangjun Yan, Xulin Li, Xuan Zhang, Di Wu, Shangping Zhao","doi":"10.1038/s41435-026-00390-6","DOIUrl":"10.1038/s41435-026-00390-6","url":null,"abstract":"The ameliorative effects of heparin on acute pancreatitis (AP) have received widespread attention. NLRP3 inflammasome-dependent pyroptosis has been reported to be a key factor contributing to AP development. However, it remains unclear whether heparin alleviates AP by modulating NLRP3 inflammasome-dependent pyroptosis. An AP model was established in vivo and in vitro using Sprague Dawley rats and AR42J cells. TUNEL and propidium iodide staining assessed cell death. Cellular pyroptosis was observed under a microscope. Intermolecular interactions were verified using Co-IP and RIP assays. The m6A level of KAT2B was assessed by MeRIP. Levels of pro-inflammatory factors were determined using ELISA. Our results showed that heparin attenuated AP in vivo by inhibiting NLRP3-mediated pyroptosis. VIRMA expression was increased in AP. Meanwhile, overexpression of VIRMA reversed the alleviating effect of heparin on cellular pyroptosis. KAT2B knockdown counteracted the promotion of pyroptosis by VIRMA. Mechanically, VIRMA promoted KAT2B mRNA stability in an m6A–ELAVL1–dependent manner, whereas KAT2B upregulation further promoted NLRP3 acetylation at K694. The wild-type NLRP3 reversed the inhibitory of heparin on pyroptosis, and KAT2B amplified this regulatory effect. Taken together, heparin prevented cellular pyroptosis by inhibiting the VIRMA-mediated m6A modification of KAT2B, which in turn inhibited NLRP3 acetylation at K694, ultimately attenuating AP.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 3","pages":"351-362"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485584","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

Increased VH4+JH6+ antibody heavy chain use in plasmablasts from asymptomatic multiple sclerosis patients 无症状多发性硬化症患者血浆中VH4+JH6+抗体重链使用增加

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-03-19 DOI: 10.1038/s41435-026-00389-z

Sara Benavides, Scott Christley, Kiel M. Telesford, Chad Smith, Katelyn Sheffer, Yipin Wu, Wei Zhang, Key M. Tse, Hannah J. Greenberg, Morgan Jackson, Caitlin Chapman, Darina Dinov, Paula Hardeman, Aksel Siva, Daniel Pelletier, Orhun Kantarci, Christine Lebrun-Frénay, Lindsay G. Cowell, Darin T. Okuda, Nancy L. Monson

{"title":"Increased VH4+JH6+ antibody heavy chain use in plasmablasts from asymptomatic multiple sclerosis patients","authors":"Sara Benavides, Scott Christley, Kiel M. Telesford, Chad Smith, Katelyn Sheffer, Yipin Wu, Wei Zhang, Key M. Tse, Hannah J. Greenberg, Morgan Jackson, Caitlin Chapman, Darina Dinov, Paula Hardeman, Aksel Siva, Daniel Pelletier, Orhun Kantarci, Christine Lebrun-Frénay, Lindsay G. Cowell, Darin T. Okuda, Nancy L. Monson","doi":"10.1038/s41435-026-00389-z","DOIUrl":"10.1038/s41435-026-00389-z","url":null,"abstract":"Radiologically isolated syndrome (RIS) is a neurological condition in people with demyelinating lesions on brain and/or spinal cord magnetic resonance imaging (MRI) studies, but without clinical symptoms of disease. Elucidating the immune profile of people with RIS (pwRIS) who will display MRI or clinical features of advancing disease is critical to our understanding of disease pathogenesis. Our lab previously identified features of B cell dysregulation in people with clinically isolated syndrome (pwCIS), who have both demyelinating lesions and a first clinical event of disease. The goal of this study was to compare features of B cell dysregulation in pwRIS, pwCIS, and healthy controls (HC). The second goal was to determine if these features of B cell dysregulation would be evident in people who meet the new MS diagnostic criteria, particularly in the context of their disease course for 5 years post-sampling. Features of plasmablast responses that distinguish pwRIS from pwCIS include PB expansion, antigen-driven selection, VH4 and JH6 antibody gene over-usage, neuron reactivity by purified IgG and individually cloned antibodies. Furthermore, VH4:JH6 pairing in plasmablasts was higher in people with stable MS who do not show changes in MRI or clinical events from those with advancing disease activity.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 3","pages":"341-350"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41435-026-00389-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Single-cell transcriptomics reveals heterogeneity and immune microenvironment in lymphatic metastasis of head and neck squamous cell carcinoma 单细胞转录组学揭示头颈部鳞状细胞癌淋巴转移的异质性和免疫微环境。

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-03-16 DOI: 10.1038/s41435-026-00392-4

Guannan Wei, Guanghao Zhang, Shan Jiang, Ce Li

{"title":"Single-cell transcriptomics reveals heterogeneity and immune microenvironment in lymphatic metastasis of head and neck squamous cell carcinoma","authors":"Guannan Wei, Guanghao Zhang, Shan Jiang, Ce Li","doi":"10.1038/s41435-026-00392-4","DOIUrl":"10.1038/s41435-026-00392-4","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) is a major health concern with considerable morbidity and mortality worldwide. Previous studies have applied single-cell sequencing to characterize the tumor microenvironment in HNSCC, providing insights into immune cell composition, stromal interactions, and malignant cell states. However, there remains a gap in analyzing lymph node metastasis (LM) and normal lymph node tissues (LN) by using single-cell RNA sequencing (scRNA-seq) analysis. We performed comparative scRNA-seq analysis on seven lymph node metastatic tissues of HNSCC patients and five non-metastatic tissues. We identified several cell types with significantly altered expression levels, such as CD8+ Tex cells, Macrophages, and Cancer-associated fibroblasts (CAFs). Tumor cells were classified into seven clusters, with cluster2 strongly linked to tumorigenesis and metastasis. Specific subsets such as CD4_Tfh_CXCL13, CD4_Treg_RPL26, CD8_teff_CREM, NK_GZMB, Macrophages_OLFML3 and macrophages_SPP1 cells were also associated with HNSCC progression and metastasis. Based on these findings, we constructed and validated a prognostic model for HNSCC using the expression of INHBA, SFRP2, SPP1, and IFI27. This model provides a tool for risk stratification and informs potential therapeutic strategies for HNSCC.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 3","pages":"323-340"},"PeriodicalIF":4.5,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467783","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

MTA1-mediated transcriptional repression of Cox2 confers resistance against neutrophil infiltration in endometritis mta1介导的Cox2转录抑制赋予子宫内膜炎对中性粒细胞浸润的抗性。

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-03-10 DOI: 10.1038/s41435-026-00391-5

Mao Li, Junting Li, Huan Li, Fang Liu, Yang Yang, Ruifang An

{"title":"MTA1-mediated transcriptional repression of Cox2 confers resistance against neutrophil infiltration in endometritis","authors":"Mao Li, Junting Li, Huan Li, Fang Liu, Yang Yang, Ruifang An","doi":"10.1038/s41435-026-00391-5","DOIUrl":"10.1038/s41435-026-00391-5","url":null,"abstract":"Abnormal accumulation of prostaglandin E2 (PGE2) is a secondary effect of the presence of bacterial infection, and usually causes overproduction of proinflammatory cytokines, thereby leading to infiltration of neutrophils, serving as a key etiology of endometritis linking to infertility. Metastasis-associated protein 1 (MTA1), functioning as a master transcriptional coregulator, is increasingly recognized as an important influencer of inflammation, but its functional roles in endometritis, if any, remain unexplored. Herein, by investigating clinical correlations, in vitro assays, and uterus-specific Mta1 knockouts, we show that MTA1 expression was significantly downregulated in endometrial biopsies from patients with chronic endometritis (CE) and in human endometrial stromal cells (HESCs) challenged with clinically relevant pathogenic dosage of lipopolysaccharide (LPS). MTA1 deletion augmented endometrial neutrophil infiltration, exacerbated inflammatory phenotype and negatively affected the outcome of LPS-induced endometritis through modulation of PGE2 secretion. We have also identified cyclooxygenase-2 (COX2) as the key rate-limiting enzyme responsible for the deregulated PGE2 synthesis in MTA1 deficiency-exacerbated endometritis. Mechanistically, MTA1 negatively regulated the transcription of Cox2, likely in collaboration with HDAC2 (histone deacetylase 2), in LPS-challenged endometrial stromal cells (ESCs). In summary, MTA1 signaling may govern appropriate inflammatory response in ESCs against the pathogenesis of endometritis.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 3","pages":"307-322"},"PeriodicalIF":4.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432426","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

Regulatory mechanisms of ALKBH5/CIITA axis in the synergistic modulation of hepatocellular carcinoma radiotherapy and immunotherapy ALKBH5/CIITA轴在肝细胞癌放疗和免疫治疗协同调节中的调控机制

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-03-10 DOI: 10.1038/s41435-026-00382-6

Fei Wang, Hui Hou, Hong Yang, Ting Dou, Zhenxia Wang, Hongdan Fu, Hong Li, Wei Zhang, Haiping Zhao, Hao Yang

{"title":"Regulatory mechanisms of ALKBH5/CIITA axis in the synergistic modulation of hepatocellular carcinoma radiotherapy and immunotherapy","authors":"Fei Wang, Hui Hou, Hong Yang, Ting Dou, Zhenxia Wang, Hongdan Fu, Hong Li, Wei Zhang, Haiping Zhao, Hao Yang","doi":"10.1038/s41435-026-00382-6","DOIUrl":"10.1038/s41435-026-00382-6","url":null,"abstract":"The prognosis for hepatocellular carcinoma remains grim. Combining radiotherapy with immune checkpoint blockade (ICB) has shown potential to enhance therapeutic outcomes, yet there is a pressing need for further advancements. Our previous research demonstrated that this combined approach suppresses ALKBH5 gene expression and increases m6A modification levels in hepatocellular carcinoma tissues. High-throughput sequencing and detailed molecular analysis revealed that inhibiting ALKBH5 amplifies CIITA m6A modifications post-therapy. This modulation triggers MHC II molecule expression in tumors, facilitating the presentation of tumor-associated antigens to CD4 + T lymphocytes and the recruitment of CD8 + T cells for an anti-tumor immune response. Building on these findings, we engineered a CIITA vector with a specific site mutation to confirm that the regulation of CIITA by the combined radiotherapy and immunotherapy is mediated through m6A methylation. Consequently, we established a comprehensive network involving ALKBH5, CIITA, MHC II, and CD4+ and CD8 + T cells. To elucidate the role and underlying molecular mechanisms of this combined therapy in reshaping the tumor immune microenvironment for hepatocellular carcinoma, we employed multi-omics approaches across in vitro, animal model, and clinical multi-dimensional studies, offering novel insights for enhancing treatment efficacy.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 3","pages":"289-306"},"PeriodicalIF":4.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41435-026-00382-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Immuno-molecular features and therapeutic implications of brain metastases in clear cell renal cell carcinoma patients 透明细胞肾细胞癌患者脑转移的免疫分子特征及治疗意义。

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-03-07 DOI: 10.1038/s41435-026-00385-3

I. Roodhooft, L. Kinget, G. Mammone, M. Baldewijns, PR Debruyne, E. Roussel, M. Albersen, O. Demeulenaere, AD Garg, PM Clement, J. Van Loon, S. De Vleeschouwer, H. Van Den Bulck, H. Vandermeulen, L. De Wever, A. Laerte, B. Beuselinck

{"title":"Immuno-molecular features and therapeutic implications of brain metastases in clear cell renal cell carcinoma patients","authors":"I. Roodhooft, L. Kinget, G. Mammone, M. Baldewijns, PR Debruyne, E. Roussel, M. Albersen, O. Demeulenaere, AD Garg, PM Clement, J. Van Loon, S. De Vleeschouwer, H. Van Den Bulck, H. Vandermeulen, L. De Wever, A. Laerte, B. Beuselinck","doi":"10.1038/s41435-026-00385-3","DOIUrl":"10.1038/s41435-026-00385-3","url":null,"abstract":"Brain metastases (BrM) in metastatic clear-cell renal cell carcinoma (m-ccRCC) are resistant to most systemic therapies, but respond better to cabozantinib. We documented intracranial response on common systemic therapies for m-ccRCC, described molecular mechanisms underlying efficacy or resistance and performed whole transcriptome sequencing on primary ccRCC-tumors and metastatic lesions in distinct host organs, including the brain. 30 patients with BrM were available for the evaluation of intracranial response on 39 systemic therapy lines. No partial responses (PR) were observed upon ipilimumab/nivolumab (0%), and pazopanib (0%). PRs were rare upon nivolumab (14%), sunitinib (25%), axitinib (28%) and axitinib/pembrolizumab (33%), but higher upon cabozantinib/nivolumab (50%) and cabozantinib in monotherapy (64%). Median time-to-intracranial-progression was the longest (not reached) with cabozantinib and cabozantinib/nivolumab and the shortest with nivolumab and ipilimumab/nivolumab (2.5 months). mRNA-expression analysis showed higher cMET- and AXL-expression in BrM compared to the primary tumor and other metastatic sites, lower angiogenesis and immune scores, less CD8 + T-cells and more M2-like (anti-inflammatory) macrophages. Based on this translational and clinical data, cabozantinib is the optimal systemic therapy for m-ccRCC patients with BrM. As the presence of BrM impacts the choice of first-line treatment, we advise to screen for BrM at baseline, even in asymptomatic patients.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 3","pages":"276-288"},"PeriodicalIF":4.5,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41435-026-00385-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Th17/Treg cell imbalance in allergic rhinitis: mechanisms and therapeutic implications 变应性鼻炎的Th17/Treg细胞失衡：机制和治疗意义

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-03-05 DOI: 10.1038/s41435-026-00378-2

Ye Xiong, Fei Wang, Ge Hu, Ting Xiao, Wenke Wu, Xiao Zhu, Tian Li, Zhenhua Zhu

{"title":"Th17/Treg cell imbalance in allergic rhinitis: mechanisms and therapeutic implications","authors":"Ye Xiong, Fei Wang, Ge Hu, Ting Xiao, Wenke Wu, Xiao Zhu, Tian Li, Zhenhua Zhu","doi":"10.1038/s41435-026-00378-2","DOIUrl":"10.1038/s41435-026-00378-2","url":null,"abstract":"Allergic rhinitis (AR) is a chronic, noninfectious inflammation of the nasal mucosa. Recent worldwide epidemiological surveys have indicated an increase in AR incidence. Recurrent allergic symptoms, disease complications and prolonged treatment have brought heavy physical and mental burdens to AR patients. AR pathogenesis is an IgE-mediated type I allergic reaction involving multiple immune cells and cytokines. The imbalance between T helper 17 cells (Th17) and regulatory cells (Tregs) plays an important role in the immune imbalance in AR. This review provides a comprehensive analysis of the immune imbalance of AR, focusing on the key role of Th17/Treg cell imbalance in the pathogenesis of diseases. In addition to exploring the potential mechanisms, this article also reviews various treatments to regulate the balance of Th17/Treg, including conventional drug treatment, traditional Chinese medicine compounds, probiotics and emerging therapies. Increasing amounts of clinical and experimental evidence confirm that restoring the Th17/Treg balance is an effective strategy for relieve AR symptoms. This study aims to promote the understanding of the disease mechanism by summarizing the regulatory role of Th17/Treg in AR, and provide valuable insights for the development of innovative treatment models.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 2","pages":"157-172"},"PeriodicalIF":4.5,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41435-026-00378-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation PANoptosis作为药物发现框架：整合细胞死亡结构与临床翻译。

IF 4.5 3区医学

Genes and immunity Pub Date : 2026-03-03 DOI: 10.1038/s41435-026-00388-0

Mohit Bhardwaj, Kirti Upmanyu, Saurabh Upadhyay

{"title":"PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation","authors":"Mohit Bhardwaj, Kirti Upmanyu, Saurabh Upadhyay","doi":"10.1038/s41435-026-00388-0","DOIUrl":"10.1038/s41435-026-00388-0","url":null,"abstract":"Programmed cell death pathways—apoptosis, pyroptosis, and necroptosis—were long regarded as discrete entities, yet mounting evidence reveals their convergence in PANoptosis, a unified inflammatory death program orchestrated by supramolecular PANoptosome complexes. By integrating upstream sensors (ZBP1, AIM2, NLRP3, Pyrin), scaffolding adaptors (ASC, RIPK1, FADD), and executioners (caspase-1/8, RIPK3–MLKL, gasdermins), PANoptosis operates as a fail-safe against pathogens and oncogenic stress, but also drives immunopathology in sterile injury, sepsis, cancer, and neurodegeneration. This review synthesizes recent advances in the molecular architecture of PANoptosis, highlighting cross-regulatory redundancies, novel modulators, and post-translational checkpoints that expand therapeutic opportunities. We provide an evidence-graded framework for pharmacological intervention, spanning small-molecule inhibitors (RIPK1, RIPK3, MLKL, caspases, NLRP3, gasdermins), biologics (IL-1β, IL-18, TNF antagonists), and nucleic acid therapeutics, with reference to active and completed clinical trials. Emphasis is placed on the Clinical Polarity and Timing Model, which distinguishes contexts where PANoptosis should be induced (apoptosis-resistant tumors) versus restrained (cytokine storm, ischemia–reperfusion injury). Emerging biomarker panels—including phosphorylated RIPK3/MLKL, gasdermin fragments, and inflammasome-derived cytokines—offer tools for patient stratification and real-time pharmacodynamic monitoring. Finally, we explore the drug discovery frontier, from covalent GSDMD antagonists and CNS-penetrant RIPK1 inhibitors to synthetic biology approaches capable of confining PANoptotic modulation to defined tissues. By integrating mechanistic insights with translational pharmacology, this review positions PANoptosis as both a therapeutic target and an adjuvant framework, outlining how its selective modulation could transform the management of infectious, inflammatory, oncologic, and neurodegenerative diseases.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 2","pages":"141-156"},"PeriodicalIF":4.5,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348282","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