Cellular &Molecular Immunology最新文献

{"title":"Correction: Cholesterol promotes autoimmune pathology through T follicular helper cells.","authors":"Wei Li, George C Tsokos","doi":"10.1038/s41423-025-01350-2","DOIUrl":"https://doi.org/10.1038/s41423-025-01350-2","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages regulate PD-1 and CTLA-4 expression on ILC2s and their responsiveness in the tumor microenvironment.","authors":"Cecilia Ciancaglini, Silvia Santopolo, Stefania Martini, Francesca Scordamaglia, Giuseppe Pietropaolo, Mattia Laffranchi, Giuseppe Sciumè, Guido Ferlazzo, Paola Vacca, Lorenzo Moretta, Linda Quatrini","doi":"10.1038/s41423-025-01347-x","DOIUrl":"https://doi.org/10.1038/s41423-025-01347-x","url":null,"abstract":"<p><p>Chronic inflammation can induce lymphocyte dysfunction, which is characterized by the expression of inhibitory immune checkpoints. For type 2 innate lymphoid cells (ILC2s), the acquisition of a state of hyporesponsiveness associated with PD-1 expression has been reported in severe allergic inflammation. However, the regulation of ILC2 reactivity in the context of cancer is less clear. The contribution of ILC2s to the antitumor immune response depends, indeed, on the type of tumor and the distinct cellular interplay within the microenvironment. Here, we show that ILC2s in malignant pleural effusions express the immune checkpoints PD-1 and CTLA-4. An in vitro model of the ILC2‒macrophage interaction demonstrated that this crosstalk is responsible for driving CTLA-4 expression and limiting ILC2 activation. Thus, by preventing ILC2 exhaustion, macrophages maintain ILC2 responsiveness to signals from the tissue. These results reveal that, unlike PD-1 expression, CTLA-4 expression on ILC2s is associated with the maintenance of a reactive state during chronic inflammation in the tumor microenvironment.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver immunology: new insights from cutting-edge technologies","authors":"Adrien Guillot,&nbsp;Bin Gao","doi":"10.1038/s41423-025-01342-2","DOIUrl":"10.1038/s41423-025-01342-2","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 10","pages":"1129-1131"},"PeriodicalIF":19.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-025-01342-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the IL-9‒NLRP3 axis in insulin resistance and adipose tissue inflammation during diet-induced obesity.","authors":"Marc P Hübner, Dennis de Coninck, Benjamin Lenz, Jayagopi Surendar, Marianne Koschel, Narcisse Victor Tchamatchoua Gandjui, Beng Amuam Andrew, Lucy Cho Nchang, Anita Obi Bate Ebob, Fanny Fri Fombad, Lisa Marie Springer, Lars Eppe, Frank A Schildberg, Samuel Wanji, Achim Hoerauf, Alexander Pfeifer, Indulekha Karunakaran","doi":"10.1038/s41423-025-01340-4","DOIUrl":"https://doi.org/10.1038/s41423-025-01340-4","url":null,"abstract":"<p><p>Despite the proven beneficial role of type 2 cytokines in diabetes and obesity, IL-9, a predominant Th2 cytokine, has not been investigated in this context. The present study characterized the role of IL-9 signaling in obesity and metabolic dysfunction. We found decreased IL-9 levels in human type 2 diabetes patients and decreased IL-9 signaling in high-fat diet (HFD)-induced obese mice. On the other hand, recombinant IL-9 (rIL-9) treatment reversed insulin insensitivity and inflammation following HFD consumption. IL-9R knockout (KO) mice fed a HFD presented faster weight gain, impaired glucose and insulin tolerance, defective insulin signaling, increased adipocyte size, and decreased energy expenditure. In the adipose tissue of HFD-fed IL-9R KO mice, a significant increase in the number of CD11c+ macrophages and a decrease in the number of RELMα+ macrophages, eosinophils and ILC2s were observed, along with increased TNF, decreased adiponectin production and increased expression of NLRP3. In vitro treatment of human and mouse macrophages with rIL-9 decreased the release of NLRP3-induced IL-1β and IL-18. In vivo treatment of HFD-fed IL-9R KO mice with a pharmacological inhibitor of the NLRP3 inflammasome rescued body weight, insulin sensitivity and adipose tissue inflammation. Mechanistically, the STAT5 protein was found to be important for the IL-9-induced inhibition of the NLRP3 inflammasome in adipose tissue. In addition, we also demonstrated a potential role for IL-9 in the protective effects of helminth immunomodulation during obesity and insulin resistance in filaria-infected humans and in an animal model. Taken together, the results of this study highlight that IL-9 signaling improves insulin signaling by inhibiting NLRP3-induced inflammation.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infiltrating macrophages replace Kupffer cells and play diverse roles in severe alcohol-associated hepatitis","authors":"Yang Wang,&nbsp;Yukun Guan,&nbsp;Dechun Feng,&nbsp;Luca Maccioni,&nbsp;Maria A. Parra,&nbsp;Brandon Peiffer,&nbsp;Bryan Mackowiak,&nbsp;Takashige Kuwabara,&nbsp;Kiyoshi Mori,&nbsp;Masashi Mukoyama,&nbsp;Ramon Bataller,&nbsp;Zhaoli Sun,&nbsp;Bin Gao","doi":"10.1038/s41423-025-01343-1","DOIUrl":"10.1038/s41423-025-01343-1","url":null,"abstract":"Patients with alcohol-associated cirrhosis (AC) may develop severe alcohol-associated hepatitis (sAH), a disease with high short-term mortality. Our previous studies demonstrated that sAH, but not AC livers, are infiltrated with a high number of self-sustaining IL-8+ neutrophils that likely drive the transition from AC to sAH. Monocyte-derived macrophages (MoMFs) also infiltrate the liver in sAH, but their roles remain largely obscure. In the present study, we characterized liver macrophages in human liver explants from sAH and AC patients. Our data revealed a marked reduction in Kupffer cells, whereas MoMFs were increased in sAH and AC. Single-cell RNA-Seq analyses revealed several populations in both AC and sAH, including C1Q+, S100A8+, APOE+, TNF+ and VSIG4+ macrophages, with sAH containing unique C1Q+ macrophages potentially playing a role in removing apoptotic neutrophils in sAH. C1Q+ macrophages also express many genes involved in phagocytosis and proinflammatory and anti-inflammatory functions, suggesting that C1Q+ macrophages have diverse functions in sAH. The roles of C1Q, S100A8, and APOE were further examined in experimental models of alcohol-induced liver injury. Our data revealed that C1q KO mice and macrophage-specific S100a8 KO mice presented similar alcohol-induced liver injury and hepatic neutrophil infiltration, while Apoe&nbsp;KO mice developed much more severe liver injury than did WT mice following chronic-plus-binge ethanol challenge. Taken together, sAH and AC are infiltrated with multiple populations of macrophages that perform diverse functions to drive chronic disease progression. Unique C1Q+ macrophages in sAH play a compensatory role in removing dead cells but may also promote inflammation in sAH.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 10","pages":"1262-1275"},"PeriodicalIF":19.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-025-01343-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial cell-ILC3 crosstalk via the ET-1/EDNRA axis promotes NKp46⁺ILC3 glycolysis to alleviate intestinal inflammation.","authors":"Xinyao Li, Yimin Chen, Junyu He, Jian Tang, Chunling Chen, Liyun Meng, Yizhuang Lu, Xiaoming Lyu, Yuxiong Guo, Yumei He","doi":"10.1038/s41423-025-01345-z","DOIUrl":"https://doi.org/10.1038/s41423-025-01345-z","url":null,"abstract":"<p><p>Communication between group 3 innate lymphoid cells (ILC3) and other immune cells, as well as intestinal epithelial cells, is pivotal in regulating intestinal inflammation. This study, for the first time, underscores the importance of crosstalk between intestinal endothelial cells (ECs) and ILC3. Our single-cell transcriptome analysis combined with protein expression detection revealed that ECs significantly increased the population of interleukin (IL)-22⁺ ILC3 through interactions mediated by endothelin-1 (ET-1) and its receptor endothelin A receptor (EDNRA). Genetic deficiency of EDNRA reduces the proportion of NKp46⁺ ILC3 and impairs IL-22 production in a T-cell-independent, cell-intrinsic manner, leading to increased intestinal inflammation. Mechanistically, the ET-1-EDNRA axis modulates hypoxia-inducible factor 1 alpha (HIF-1α) through protein kinase B (AKT) signaling, supporting metabolic adaptation toward glycolysis and providing protection against colitis. Moreover, restoring HIF-1α expression or providing exogenous lactate can alleviate colitis associated with EDNRA deficiency and ILC3 glycolytic dysfunction. These findings underscore the importance of communication between intestinal ECs and ILC3 via the ET-1-EDNRA axis in metabolic adaptation processes within ILC3 and maintaining intestinal homeostasis.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The STING/type I interferon axis drives the interplay between marginal zone B cells and T follicular helper cells in Sjögren's disease.","authors":"Yacun Chen, Sulan Yu, Philip Hei Li, Haozhen Yan, Jing Xie, Iris Yanki Tang, Hongyun Cheng, Xiang Lin","doi":"10.1038/s41423-025-01346-y","DOIUrl":"https://doi.org/10.1038/s41423-025-01346-y","url":null,"abstract":"<p><p>Type I interferon (IFN-I) is highly prevalent in autoimmune disorders and is intricately involved in disease pathogenesis, including Sjögren's disease (SjD), also known as Sjögren's syndrome. Although the T follicular helper (Tfh) cell response has been shown to drive SjD development in a mouse model of experimental Sjögren's syndrome (ESS), the connection between IFN-I and the Tfh cell response remains unclear. As the activation of stimulator of interferon genes (STING) induces IFN-I production, we first demonstrated that mice deficient in STING or IFN-I signaling presented diminished Tfh cells and were completely resistant to ESS development. However, the STING-IFN-I axis does not directly influence Tfh cell differentiation. Instead, IFN-I signaling in B cells was essential for mounting Tfh cell responses, as evidenced in Cd19CreIfnar1flox mice, which also showed resistance to ESS development. Mechanistic analyses revealed that IFN-I drove CXCR5 expression in innate-like marginal zone B cells via the MEKK3-OCT2 axis, facilitating their migration into the follicular area. Additionally, IFN-I promoted interleukin-6 production in B cells via the MEKK3-ERK5 axis, resulting in hyperactive Tfh cell responses. In SjD patients, STING activation was predominantly observed in circulating CD14+ monocytes and was positively correlated with disease activity and effector T-cell responses. Pharmaceutical inhibition of either STING or IFNAR1 yielded moderate improvements in ESS mice with chronic inflammation, but combination therapy markedly improved outcomes and led to signs of disease remission. Our findings elucidate a novel mechanism by which IFN-I bridges innate and Tfh cell responses, suggesting new therapeutic avenues for SjD and related autoimmune disorders.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoration of the peace in autoimmune disease: tired of fighting?","authors":"Derk Amsen","doi":"10.1038/s41423-025-01335-1","DOIUrl":"10.1038/s41423-025-01335-1","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 10","pages":"1276-1278"},"PeriodicalIF":19.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FBXW7 is a multifaceted regulator of the innate immune response to DNA viruses.","authors":"Xue-Dan Sun, Jia-Li Wang, Xin-Yu Zhang, Zi-Lun Ruan, Wei Liang, Yi Guo, Wei-Tao Guan, Qing Yang, Ling Li, Hong-Bing Shu, Ming-Ming Hu","doi":"10.1038/s41423-025-01336-0","DOIUrl":"https://doi.org/10.1038/s41423-025-01336-0","url":null,"abstract":"<p><p>Upon DNA virus infection, cGAS senses viral DNA and triggers MITA (also called STING)-dependent induction of type I interferons (IFN-Is) and other cytokines/chemokines. IFN-Is further activate STAT1/2 to induce interferon-stimulated genes (ISGs) and the innate antiviral response. How the innate antiviral response is silenced in uninfected cells and efficiently mounts upon viral infection is not fully understood. In this study, we found that FBXW7, a substrate recognition component of the SCF E3 ubiquitin ligase complex, is a multifaceted regulator of the innate immune response to DNA viruses. In uninfected cells, FBXW7 mediates the polyubiquitination and degradation of GSK3α/β-phosphorylated SLC35B2/3 at the Golgi apparatus. This leads to the downregulation of sulfated glycosaminoglycans (sGAGs) in the Golgi apparatus and the inactivation of MITA in uninfected cells. In addition, FBXW7 mediates the degradation of GSK3α/β-phosphorylated MYC, which is a repressor of STAT1/2, leading to proper STAT1/2 levels in uninfected cells. The differential regulation of FBXW7 on MITA and STAT1/2 ensures inactivation but is ready for fast mount of the innate immune response in uninfected cells. Infection with DNA viruses activates the PI3K‒AKT axis, which inactivates GSK3α/β and inhibits FBXW7-mediated polyubiquitination and degradation of SLC35B2/3, leading to increased production of sGAGs, activation of MITA and rapid onset of the innate antiviral response. Consistently, gene disruption experiments indicate that FBXW7 modulates the innate antiviral response in human THP-1 and mouse BMDM cells. These findings suggest that FBXW7 functions as a versatile regulator of the innate immune response to DNA viruses by differentially regulating upstream and downstream components of the type I interferon induction loop.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal taurine acts as a novel immunometabolic modulator of IBD by degrading redundant mitochondrial RNA.","authors":"Le-Xi Wu, Jia-Huan Xie, Jie-Yu Li, Wen-Ping Li, Xin-Tao Mao, Ling-Jie Huang, Hao-Tian Chen, Jiang-Yan Zhong, Li-Min Lin, Shicheng Su, Yi-Yuan Li, Qian Cao, Jin Jin","doi":"10.1038/s41423-025-01344-0","DOIUrl":"https://doi.org/10.1038/s41423-025-01344-0","url":null,"abstract":"<p><p>Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD) is hampered by issues of nonresponse and resistance, highlighting the urgent need for alternative or complementary treatments. Our study revealed significant upregulation of taurine in the intestinal tissues of IBD patients, which was inversely related to the severity of the disease. A key discovery was that TNF directly induced taurine synthesis in intestinal epithelial cells and increased the production of angiogenin, a nuclease that degrades mitochondrial RNA, which is known to amplify inflammatory responses. By degrading mitochondrial RNA, angiogenin inhibits the inflammatory response in macrophages, suggesting a potent immune-modulatory role for taurine. This mechanism implies that taurine could serve as an adjunct to anti-TNF therapies, enhancing their efficacy and providing a novel strategy for the management of IBD and other chronic inflammatory diseases by harnessing the body's innate immune regulatory mechanisms.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}