International immunology最新文献_第3页

Immune responses underpinning acute co-infections with unrelated viruses: timing and location matter. 支持与不相关病毒急性合并感染的免疫反应：时间和地点问题。

IF 3.2 4区医学

International immunology Pub Date : 2025-08-04 DOI: 10.1093/intimm/dxaf018

Isabelle Jia Hui Foo, Lukasz Kedzierski, Katherine Kedzierska

{"title":"Immune responses underpinning acute co-infections with unrelated viruses: timing and location matter.","authors":"Isabelle Jia Hui Foo, Lukasz Kedzierski, Katherine Kedzierska","doi":"10.1093/intimm/dxaf018","DOIUrl":"10.1093/intimm/dxaf018","url":null,"abstract":"Immunity to viral infections is generally studied in isolation by measuring immune responses towards a single virus. However, concurrent or sequential viral co-infections can occur in a single host. Viral co-infections can impact anti-viral immunity by altering protective responses and driving immunopathology. Understanding immune mechanisms towards co-infections with unrelated viruses is highly relevant to treatment and prevention. There is, however, a paucity of data on immune responses towards viral co-infections, especially with unrelated viruses. Most commonly studied viral co-infections include chronic viruses, such as hepatitis B, hepatitis C, and human immunodeficiency virus, as well as viruses infecting the same tissues, including respiratory viral co-infections. However, the immunological consequences of co-infections with unrelated acute viruses are less understood, especially for viruses affecting different anatomical sites. As co-infecting viruses can have a more pronounced impact on human health compared to infection with a single virus, understanding immune responses and, especially, the impact of timing, sequence, and location of viral co-infections is of key importance. This review provides an overview of the current knowledge on acute viral co-infections with unrelated viruses, underpinning immune mechanisms, and implications for vaccination regimens.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"507-515"},"PeriodicalIF":3.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700019","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

Central compartment of nasal cavity-derived MMP-9 enhances mixed-type 2 inflammation in eosinophilic chronic rhinosinusitis. 鼻腔中央隔室来源的MMP-9增强嗜酸性慢性鼻窦炎的混合2型炎症。

IF 3.2 4区医学

International immunology Pub Date : 2025-08-04 DOI: 10.1093/intimm/dxaf025

Takeshi Tsuda, Soichiro Fujii, Sho Obata, Kazuya Takeda, Masaki Hayama, Yohei Maeda, Ayaka Nakatani, Naoki Umeda, Miyu Saito, Kentaro Fujii, Toshihiro Kishikawa, Hidenori Tanaka, Kiyohito Hosokawa, Takashi Sato, Yukinori Takenaka, Daisuke Okuzaki, Satoshi Nojima, Masaru Ishii, Hidenori Inohara

{"title":"Central compartment of nasal cavity-derived MMP-9 enhances mixed-type 2 inflammation in eosinophilic chronic rhinosinusitis.","authors":"Takeshi Tsuda, Soichiro Fujii, Sho Obata, Kazuya Takeda, Masaki Hayama, Yohei Maeda, Ayaka Nakatani, Naoki Umeda, Miyu Saito, Kentaro Fujii, Toshihiro Kishikawa, Hidenori Tanaka, Kiyohito Hosokawa, Takashi Sato, Yukinori Takenaka, Daisuke Okuzaki, Satoshi Nojima, Masaru Ishii, Hidenori Inohara","doi":"10.1093/intimm/dxaf025","DOIUrl":"10.1093/intimm/dxaf025","url":null,"abstract":"Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper respiratory tract. Although previously classified based on the presence or absence of nasal polyps, it is now commonly classified by endotype. Eosinophilic CRS (ECRS) is based on type 2 inflammation and the formation of intractable nasal polyps with eosinophil infiltration. Endoscopic surgery is the preferred treatment modality; however, recurrent cases are common. The central compartment of the nasal cavity has been implicated in these recurrences. Notably, the middle turbinate is considered crucial, but discussions have primarily focused on its anatomical significance. To date, there lacks a biochemical perspective on the role of the middle turbinate in recurrence. In this study, we evaluated the role of the middle turbinate as a source of inflammation in ECRS. Differences in gene expression between ECRS and non-ECRS (NECRS) middle turbinates were evaluated using RNA sequencing. Gene changes induced by MMP-9 stimulation of human nasal epithelial cells were also evaluated by RNA sequencing. Comprehensive analysis showed an enhanced IL-4 signaling pathway in the ECRS middle turbinate. Additionally, gene expression of matrix metalloproteinase-9 (MMP-9) was higher in the middle turbinates of patients with ECRS than in those with NECRS (P = .002). Furthermore, MMP-9 has been found to act on human nasal epithelial cells to enhance pathways such as IL-17, IL-6, and S100 family signaling. MMP-9 in the central compartment of the nasal cavity exacerbates ECRS by induction mixed-type 2 inflammation and airway remodeling.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"551-561"},"PeriodicalIF":3.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Immunogenomic precision medicine: a personalized approach based on immunogenomic cancer evolution. 免疫基因组精准医学：基于免疫基因组癌症进化的个性化方法。

IF 3.2 4区医学

International immunology Pub Date : 2025-08-04 DOI: 10.1093/intimm/dxaf020

Yusaku Momoi, Shogo Kumagai, Hiroyoshi Nishikawa

{"title":"Immunogenomic precision medicine: a personalized approach based on immunogenomic cancer evolution.","authors":"Yusaku Momoi, Shogo Kumagai, Hiroyoshi Nishikawa","doi":"10.1093/intimm/dxaf020","DOIUrl":"10.1093/intimm/dxaf020","url":null,"abstract":"Cancer progression can be understood as a process of diversification and selection (the evolutionary theory of cancer). The immune system also plays a critical role in this process of diversification and selection. The cancer immunoediting hypothesis provides a partial explanation of this evolutionary process; immune-evading cancer clones with genomic and/or epigenomic alterations are selected under the pressure of immune surveillance and immunosuppressive mechanisms are equipped, leading to the development of clinically apparent cancers. Indeed, inflammatory cancers equip immunosuppressive mechanisms in response to the pressure of the immune system. However, recent studies focusing on human cancers have revealed that certain non-inflammatory cancers, which often harbor a single-driver oncogenic mutation, are equipped with immunosuppressive machinery sufficient to evade immune surveillance at the time of malignant transformation. The sequential model of the cancer immunoediting hypothesis is inadequate to explain the development of these non-inflammatory cancers, highlighting the need for a novel concept that can explain their co-evolutionary processes. Moreover, inhibition of oncogenic signaling by specific driver oncogenes has been shown not only to kill cancer cells but also to augment antitumor immunity, suggesting the potential for the advent of molecularly targeted reagents with a variety of immunomodulatory functions from the perspective of personalized therapies. Here, we discuss the processes by which cancer cells and the immune system co-evolve to establish clinically apparent cancers, thereby introducing a new concept of 'immunogenomic cancer evolution', that provides a rationale for the potential of 'immunogenomic cancer precision medicine'.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"517-537"},"PeriodicalIF":3.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Differential regulation of type I and II interferon signals by the transcription factor interferon regulatory factor-2 for the generation and function of macrophage populations in the liver. 转录因子IRF-2对I型和II型干扰素信号在肝脏巨噬细胞群产生和功能中的差异调节

IF 3.2 4区医学

International immunology Pub Date : 2025-08-04 DOI: 10.1093/intimm/dxaf024

Kazuki Yoshizawa, Yuta Yamamoto, Masaya Takamoto, Yoh-Ichi Tagawa, Yuji Soejima, Hideki Sanjo, Shinsuke Taki

{"title":"Differential regulation of type I and II interferon signals by the transcription factor interferon regulatory factor-2 for the generation and function of macrophage populations in the liver.","authors":"Kazuki Yoshizawa, Yuta Yamamoto, Masaya Takamoto, Yoh-Ichi Tagawa, Yuji Soejima, Hideki Sanjo, Shinsuke Taki","doi":"10.1093/intimm/dxaf024","DOIUrl":"10.1093/intimm/dxaf024","url":null,"abstract":"Two major macrophage populations in the steady-state liver, resident Kupffer cells (KCs) and monocyte-derived macrophages (MoMFs), contribute crucially to the unique physiological functions of the organ. Much remains to be learned, however, about how the differentiation and functions of these cell populations are regulated. We found here that Ly6C-MHCII+ MoMFs were severely reduced in mice lacking interferon (IFN) regulatory factor-2 (IRF-2) (Irf2-/- mice) but restored to the normal frequencies by introducing type I IFN receptor deficiency, indicating that IRF-2 supports MoMF differentiation through attenuating excess type I IFN signals. On the other hand, Irf2-/- KCs developed normally but lacked MHC class II (MHCII) expression. Similar MHCII deficiency in KCs in Il15-/- and Ifng-/- but not Rag1-/- mice pointed to the role for NK cell-derived IFN-γ. Indeed, MHCII expression on resident KCs in Ifng-/- mice was recovered via wild-type NK cells that circulated upon parabiosis as well as by administration of IFN-γ. In contrast, parabiotic restoration of NK cell deficiency in Irf2-/- mice failed to elevate MHCII expression on KCs. Furthermore, Irf2-/- KCs required several times higher amounts of IFN-γ to upregulate MHCII expression than Ifng-/- KCs. Thus, IRF-2 maintains steady-state MHCII expression on KCs by potentiating IFN-γ responses of KCs. Collectively, our current study revealed that IRF-2 plays critical roles in the establishment of the steady state hepatic macrophage system through negative and positive regulation of type I IFN and IFN-γ signaling, respectively.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"539-549"},"PeriodicalIF":3.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

SLAMF6 regulates basal T cell receptor signaling and influences invariant natural killer T cell lineage diversity. SLAMF6调节基础T细胞受体信号传导并影响不变的自然杀伤T细胞谱系多样性。

IF 3.2 4区医学

International immunology Pub Date : 2025-08-04 DOI: 10.1093/intimm/dxaf030

Yukihiro Endo, Ichita Hasegawa, Akemi Igi, Atsushi Onodera, Satomi Mita, Koichi Higashi, Ken Kurokawa, Atsushi Toyoda, Masahiro Kiuchi, Miho Shinzawa, Yangsong Wang, Ryo Koyama-Nasu, Kiyoshi Hirahara, Shinichiro Motohashi, Toshinori Nakayama, Motoko Y Kimura

{"title":"SLAMF6 regulates basal T cell receptor signaling and influences invariant natural killer T cell lineage diversity.","authors":"Yukihiro Endo, Ichita Hasegawa, Akemi Igi, Atsushi Onodera, Satomi Mita, Koichi Higashi, Ken Kurokawa, Atsushi Toyoda, Masahiro Kiuchi, Miho Shinzawa, Yangsong Wang, Ryo Koyama-Nasu, Kiyoshi Hirahara, Shinichiro Motohashi, Toshinori Nakayama, Motoko Y Kimura","doi":"10.1093/intimm/dxaf030","DOIUrl":"10.1093/intimm/dxaf030","url":null,"abstract":"Invariant natural killer T (iNKT) cells differentiate into at least three distinct subsets within the thymus, with each subset's frequency varying considerably among mouse strains; however, the molecular mechanisms involved remain unclear. We herein report that iNKT cell lineage diversity results from the significant expansion of iNKT2 cells with limited T cell receptor (TCR) diversity in BALB/c mice and the selection of iNKT1 cells with significantly diverse TCRs in B6 mice. Furthermore, signaling lymphocytic-activation molecule family 6 (SLAMF6) expression on immature thymocytes significantly differs among mouse strains, with the low expression of SLAMF6 on BALB/c immature thymocytes resulting in high \"basal TCR signaling\" in preselected DP thymocytes, associated with iNKT cell expansion. Our data suggest that the expression level of SLAMF6 on immature thymocytes affects basal TCR signaling in preselected DP thymocytes, which may influence thymocyte development in a T-cell subset.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"563-577"},"PeriodicalIF":3.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Folic acid supplementation during pregnancy alleviates food allergy in offspring by inhibiting mast cell degranulation. 怀孕期间补充叶酸可通过抑制肥大细胞脱颗粒减轻后代的食物过敏。

IF 3.2 4区医学

International immunology Pub Date : 2025-08-01 DOI: 10.1093/intimm/dxaf042

Qianwei Wang, Yuchi Jiang, Sufang Duan, Ignatius Man-Yau Szeto, Huilian Che, Changqi Liu, Xiaohui Guo

{"title":"Folic acid supplementation during pregnancy alleviates food allergy in offspring by inhibiting mast cell degranulation.","authors":"Qianwei Wang, Yuchi Jiang, Sufang Duan, Ignatius Man-Yau Szeto, Huilian Che, Changqi Liu, Xiaohui Guo","doi":"10.1093/intimm/dxaf042","DOIUrl":"https://doi.org/10.1093/intimm/dxaf042","url":null,"abstract":"Studies have been exploring the connection between vitamins intake and development of food allergy, with a particular focus on folic acid (FA). However, the impact of FA supplementation on food allergy remains a subject of debate. In the present study, the anti-allergic properties of FA and its possible mechanism of action were investigated. In a Brown Norway rat food allergy model, we found that FA downregulated the expressions of specific antibodies, while influencing the Th1/Th2 balance. Furthermore, FA was found to reduce the release of particulate matters such as histamine and mast cell proteinase. Transcriptomic analysis provided evidence that FA intervention could reverse gene expression changes induced by food allergies. The gene Hsp90, responsible for producing heat shock proteins (HSP), emerged as a potential key gene involved in the process. In vitro RBL-2H3 cell-based assays suggested that FA might affect HSP90 expression through the glucocorticoid receptor (GR), leading to a reduction in effector cell degranulation. Overall, the results of this study indicate that FA has an alleviating effect on food allergies, with high doses of FA exhibiting more pronounced effects. Moreover, FA's impact on HSP90 expression through GR seems to contribute to a decrease in degranulation during the effector phase.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Immunological memory in natural killer cells. 自然杀伤细胞的免疫记忆。

IF 4.8 4区医学

International immunology Pub Date : 2025-07-22 DOI: 10.1093/intimm/dxaf016

Tsukasa Nabekura

{"title":"Immunological memory in natural killer cells.","authors":"Tsukasa Nabekura","doi":"10.1093/intimm/dxaf016","DOIUrl":"10.1093/intimm/dxaf016","url":null,"abstract":"Immune cells are classified into adaptive and innate immune cells. Adaptive immune cells-i.e. T cells and B cells-respond to pathogens in an antigen-specific manner and then provide immunological memory, contributing to long-term host defense against reinfection. In contrast, innate immune cells promptly respond to pathogens, but they are short-lived and have been thought not to contribute to immunological memory. Natural killer (NK) cells are lymphocytes essential for controlling viral infections and cancer. NK cells-which have traditionally been classified as innate immune cells-have recently been revealed as being capable of differentiating into memory NK cells, thus participating in immunological memory, formerly considered to be restricted to adaptive immune cells. Like memory T and B cells, memory NK cells (i) can be long-lived; (ii) display distinct phenotypes from naïve and activated NK cells; (iii) show augmented cellular functions, as compared with naïve NK cells; (iv) have secondary proliferation capacity; and (v) confer an improved host defense when transferred to naïve recipients. Therefore, at least in a broad sense, they fulfill the definition of immunological memory. In this article, I provide an overview of NK cell memory and recent research trends regarding this phenomenon.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"435-443"},"PeriodicalIF":4.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

B10 cells promote pro-resolving macrophage function through direct cell-cell contact and IL-10 secretion in Raw 264.7 cells. 在Raw 264.7细胞中，B10细胞通过细胞间的直接接触和IL-10的分泌，促进巨噬细胞的促溶解功能。

IF 4.8 4区医学

International immunology Pub Date : 2025-07-22 DOI: 10.1093/intimm/dxaf012

Takumi Memida, Elaheh Dalir Abdolahinia, Guoqin Cao, Sunniva Ruiz, Shengyuan Huang, Satoru Shindo, Shin Nakamura, Jiang Lin, Toshihisa Kawai, Xiaozhe Han

{"title":"B10 cells promote pro-resolving macrophage function through direct cell-cell contact and IL-10 secretion in Raw 264.7 cells.","authors":"Takumi Memida, Elaheh Dalir Abdolahinia, Guoqin Cao, Sunniva Ruiz, Shengyuan Huang, Satoru Shindo, Shin Nakamura, Jiang Lin, Toshihisa Kawai, Xiaozhe Han","doi":"10.1093/intimm/dxaf012","DOIUrl":"10.1093/intimm/dxaf012","url":null,"abstract":"It is well known that regulatory B cells (Breg), especially IL-10-producing regulatory cells (B10), play an important role in immune regulation during inflammatory and infectious diseases. Although it has been revealed that the immune regulatory function of B10 can be exerted through cognate cell-cell contact with T cells, more research is needed to delineate its impact on other key cellular immune components within the immune microenvironment. In this study, we evaluated the effect of B10 on the phenotypic change of macrophages and their pro-resolving functional activities using various co-culture systems. The roles of cell-cell contact and the IL-10 secretion by B10 on macrophage differentiation and function were determined. Splenocyte-derived B10 cells from wild-type or IL-10 knockout (KO) mice were co-cultured with RAW 264.7 cells in the presence or absence of trans-well inserts. Macrophage polarization, programmed cell death 1 (PD-1) expression, production of specialized pro-resolving mediators (SPMs), and phagocytic activity were evaluated. The results showed that direct B10-macrophage co-culture enhanced the macrophage polarization towards a pro-resolving phenotype and their PD-1 expression, which was diminished when the cultured B10 and macrophages were separated by trans-well inserts, or when B cells from IL-10 KO mice were used for the co-culture. In addition, B10 was found to promote the release of specific SPM [resolvin D series 5 (RvD5)] and phagocytic activity by macrophages after co-culture. These effects were compromised in trans-well co-culture or co-cultures with IL-10-deficient B cells. Our results suggest that B10 promotes pro-resolving macrophage differentiation and function through direct cell-cell contact and IL-10 secretion.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"457-474"},"PeriodicalIF":4.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Proteasome dysfunction in T cells causes immunodeficiency via cell cycle disruption and apoptosis. T细胞中的蛋白酶体功能障碍通过细胞周期破坏和细胞凋亡导致免疫缺陷。

IF 4.8 4区医学

International immunology Pub Date : 2025-07-22 DOI: 10.1093/intimm/dxaf021

Erkhembayar Shinebaatar, Junko Morimoto, Rinna Koga, Thanh Nam Nguyen, Yuki Sasaki, Shigenobu Yonemura, Hidetaka Kosako, Koji Yasutomo

{"title":"Proteasome dysfunction in T cells causes immunodeficiency via cell cycle disruption and apoptosis.","authors":"Erkhembayar Shinebaatar, Junko Morimoto, Rinna Koga, Thanh Nam Nguyen, Yuki Sasaki, Shigenobu Yonemura, Hidetaka Kosako, Koji Yasutomo","doi":"10.1093/intimm/dxaf021","DOIUrl":"10.1093/intimm/dxaf021","url":null,"abstract":"Proteasomes are essential molecular complexes that regulate intracellular protein homeostasis by selectively degrading ubiquitinated proteins. Genetic mutations in proteasome subunits lead to proteasome-associated autoinflammatory syndromes (PRAAS) characterized by autoinflammation, partial progressive lipodystrophy, and, in certain cases, immunodeficiency. However, the molecular mechanisms by which proteasome dysfunction results in these phenotypes remain unclear. Here, we established a mouse model carrying a mutation in β5i (encoded by Psmb8) along with T-cell-specific β5 (encoded by Psmb5) deficiency (KIKO mice). The KIKO mice presented severe loss of mature T cells in the spleen but not in the thymus, with reduced proteasome activity leading to the accumulation of ubiquitinated proteins. The CD4+ T cells of KIKO mice presented impaired proliferative activity with cell cycle arrest in the G0/G1 phase following T cell receptor (TCR) engagement. T cells from KIKO mice underwent rapid cell death through apoptosis, as treatment of T cells with the caspase inhibitor Z-Val-Ala-Asp(Ome)-fluoromethylketone (Z-VAD-FMK) rescued cell viability. Moreover, proteasome dysfunction induced apoptosis in T cells without affecting either mitochondrial functions or endoplasmic reticulum (ER) stress responses. Thus, our data provide insight into the molecular mechanisms underlying not only immunodeficiency in PRAAS patients but also T-cell deficiency associated with other disorders.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"493-505"},"PeriodicalIF":4.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015033","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

Tertiary lymphoid structures: chronic inflammatory microenvironments in kidney diseases. 三级淋巴样结构：肾脏疾病的慢性炎症微环境。

IF 4.8 4区医学

International immunology Pub Date : 2025-07-22 DOI: 10.1093/intimm/dxaf017

Takahisa Yoshikawa, Motoko Yanagita

{"title":"Tertiary lymphoid structures: chronic inflammatory microenvironments in kidney diseases.","authors":"Takahisa Yoshikawa, Motoko Yanagita","doi":"10.1093/intimm/dxaf017","DOIUrl":"10.1093/intimm/dxaf017","url":null,"abstract":"Chronic kidney disease is a global health problem with high morbidity and mortality rates. Acute kidney injury substantially increases the risk of chronic kidney disease progression, particularly in the elderly, partly because of prolonged inflammation that exacerbates kidney fibrosis and dysfunction. Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates that develop in non-lymphoid organs during chronic inflammation, such as autoimmune diseases, cancers, and age-related inflammation. Age-dependent TLS formation is observed in various organs, such as the kidneys, bladder, lacrimal glands, and liver, potentially contributing to age-related disorders, including chronic kidney disease progression after acute kidney injury. TLSs contain heterogeneous cell populations, such as T cells, B cells, pro-inflammatory fibroblasts, and blood and lymphatic vessels, which orchestrate TLS development and expansion through intensive cell-cell interactions. Pro-inflammatory fibroblasts within TLSs drive TLS formation by producing various chemokines and cytokines that recruit and activate immune cells. Additionally, the CD153-CD30 signaling pathway between senescence-associated T cells and age-associated B cells, both of which increase with age, are essential for renal TLS maturation and expansion, which could be a promising therapeutic target in kidney injury in aged individuals. TLSs also develop in human kidney diseases, such as various glomerulopathies, transplanted kidneys, and renal cell carcinomas, thereby influencing patient outcomes. This review highlights the recent advances in our understanding of the cellular and molecular mechanisms underlying TLS development and pathogenicity, with a focus on age-dependent TLSs in the kidneys. Furthermore, the clinical relevance of TLSs in human kidney diseases is discussed.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"445-455"},"PeriodicalIF":4.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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