Immunology最新文献

{"title":"T cell-intrinsic PKD3 fine-tunes differentiation into CD8+ central memory T cells and CD8 single positive thymocyte development","authors":"Jiří Koutník,&nbsp;Sebastian Peer,&nbsp;Dominik Humer,&nbsp;Grzegorz Sumara,&nbsp;Michael Leitges,&nbsp;Gottfried Baier,&nbsp;Kerstin Siegmund","doi":"10.1111/imm.13804","DOIUrl":"10.1111/imm.13804","url":null,"abstract":"<p>Members of the Protein kinases D (PKD) family are described as regulators of T cell responses. From the two T cell-expressed isoforms PKD2 and PKD3, so far mainly the former was thoroughly investigated and is well understood. Recently, we have investigated also PKD3 using conventional as well as conditional T cell-specific knockout models. These studies suggested PKD3 to be a T cell-extrinsic regulator of the cells' fate. However, these former model systems did not take into account possible redundancies with the highly homologous PKD2. To overcome this issue and thus properly unravel PKD3's T cell-intrinsic functions, here we additionally used a mouse model overexpressing a constitutively active isoform of PKD3 specifically in the T cell compartment. These transgenic mice showed a slightly higher proportion of central memory T cells in secondary lymphoid organs and blood. This effect could not be explained via differences upon polyclonal stimulation in vitro, however, may be connected to the observed developmental aberrances in the CD8 single positive compartment during thymic development. Lastly, the observed alterations in the CD8⁺ T cell compartment did not impact proper immune response upon immunization with ovalbumin or in a subcutaneous tumour model suggesting only a small to absent biological relevance. Taking together the knowledge of all our published studies on PKD3 in the T cell compartment, we now conclude that T cell-intrinsic PKD3 is a fine-tuner of central memory T cell as well as CD8 single positive thymocyte development.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"125-140"},"PeriodicalIF":4.9,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13804","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154644","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}

{"title":"Involvement of Janus kinase-dependent Bcl-xL overexpression in steroid resistance of group 2 innate lymphoid cells in asthma","authors":"Hayato Shimora,&nbsp;Masaya Matsuda,&nbsp;Yukiko Nakayama,&nbsp;Hiroto Maeyama,&nbsp;Ryunosuke Tanioka,&nbsp;Yoshiyuki Tanaka,&nbsp;Kazuyuki Kitatani,&nbsp;Takeshi Nabe","doi":"10.1111/imm.13805","DOIUrl":"10.1111/imm.13805","url":null,"abstract":"<p>The mechanisms underlying the development of steroid resistance in asthma remain unclear. To establish whether as well as the mechanisms by which the activation of Janus kinases (JAKs) is involved in the development of steroid resistance in asthma, murine steroid-resistant models of the proliferation of group 2 innate lymphoid cells (ILC2s) in vitro and asthmatic airway inflammation in vivo were analysed. ILC2s in the lungs of BALB/c mice were sorted and then incubated with IL-33, thymic stromal lymphopoietin (TSLP), and/or IL-7 with or without dexamethasone (10 nM), the pan-JAK inhibitor, delgocitinib (1–10 000 nM), and/or the Bcl-xL inhibitor, navitoclax (1–100 nM), followed by the detection of viable and apoptotic cells. The anti-apoptotic factor, Bcl-xL was detected in ILC2s by flow cytometry. As a steroid-resistant asthma model, ovalbumin (OVA)-sensitized BALB/c mice were intratracheally challenged with OVA at a high dose of 500 μg four times. Dexamethasone (1 mg/kg, i.p.), delgocitinib (3–30 mg/kg, p.o.), or navitoclax (30 mg/kg, p.o.) was administered during the challenges. Cellular infiltration into the lungs was analysed by flow cytometry. Airway remodelling was histologically evaluated. The following results were obtained. (1) Cell proliferation concomitant with a decrease in apoptotic cells was induced when ILC2s were cultured with TSLP and/or IL-7, and was potently inhibited by dexamethasone. In contrast, when the culture with TSLP and IL-7 was performed in the presence of IL-33, the proliferative response exhibited steroid resistance. Steroid-resistant ILC2 proliferation was suppressed by delgocitinib in a concentration-dependent manner. (2) The culture with IL-33, TSLP, and IL-7 induced the overexpression of Bcl-xL, which was clearly inhibited by delgocitinib, but not by dexamethasone. When ILC2s were treated with navitoclax, insensitivity to dexamethasone was significantly cancelled. (3) The development of airway remodelling and the infiltration of ILC2s into the lungs in the asthma model were not suppressed by dexamethasone, but were dose-dependently inhibited by delgocitinib. Combination treatment with dexamethasone and either delgocitinib or navitoclax synergistically suppressed these responses. Therefore, JAKs appear to play significant roles in the induction of steroid resistance by up-regulating Bcl-xL in ILC2s. The inhibition of JAKs and Bcl-xL has potential as pharmacotherapy for steroid-resistant asthma, particularly that mediated by ILC2s.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"653-668"},"PeriodicalIF":4.9,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086744","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}

{"title":"High common-γ cytokine receptor levels promote expression of Interleukin-2/Interleukin-7 receptor α-chains with implications on T-cell differentiation and function","authors":"Ju-Young Kim,&nbsp;Ertan Mayatepek,&nbsp;Julia Seyfarth,&nbsp;Marc Jacobsen","doi":"10.1111/imm.13800","DOIUrl":"10.1111/imm.13800","url":null,"abstract":"<p>Cytokines of the common-γ receptor chain (γ_c) family are crucial for T-cell differentiation and dysregulation of γ_c cytokine pathways is involved in the pathogenesis of autoimmune diseases. There is increasing evidence that the availability of the γ_c receptor (CD132) for the associated receptor chains has implications for T-cell functions. Here we studied the influence of differential γ_c expression on the expression of the IL-2Rα (CD25), the IL-7Rα (CD127) and the differentiation of activated naïve T cells. We fine-tuned the regulation of γ_c expression in human primary naïve T cells by lentiviral transduction using small hairpin (sh)RNAs and γ_c cDNA. Differential γ_c levels were then analysed for effects on T-cell phenotype and function after activation. Differential γ_c expression markedly affected IL-2Rα and IL-7Rα expression on activated naïve T cells. High γ_c expression (γ_c-high) induced significantly higher expression of IL-2Rα and re-expression of IL-7Rα after activation. Inhibition of γ_c caused lower IL-2Rα/IL-7Rα expression and impaired proliferation of activated naïve T cells. In contrast, γ_c-high T cells secreted significantly higher concentrations of effector cytokines (i.e., IFN-γ, IL-6) and showed higher cytokine-receptor induced STAT5 phosphorylation during initial stages as well as persistently higher pSTAT1 and pSTAT3 levels after activation. Finally, accelerated transition towards a CD45RO expressing effector/memory phenotype was seen especially for CD4⁺ γ_c-high naïve T cells. These results suggested that high expression of γ_c promotes expression of IL-2Rα and IL-7Rα on activated naïve T cells with significant effects on differentiation and effector cytokine expression.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"93-105"},"PeriodicalIF":4.9,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13800","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079581","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}

{"title":"Paxbp1 is indispensable for the maintenance of peripheral CD4 T cell homeostasis","authors":"Wenting Li,&nbsp;Yang Yang,&nbsp;Fan Zhuo,&nbsp;Shenglin Liu,&nbsp;Kaoyuan Zhang,&nbsp;Wei Zhang,&nbsp;Cong Huang,&nbsp;Bo Yu","doi":"10.1111/imm.13802","DOIUrl":"10.1111/imm.13802","url":null,"abstract":"<p>The size and condition of the peripheral CD4 T cell population determine the capacity of the immune response. Under homeostatic conditions, the size of the peripheral CD4 T cell population is maintained through turnover and survival. However, the underlying mechanisms remain inadequately understood. Here, we observed a significant decrease in the percentage of CD4 T cells in the periphery following the targeted deletion of the <i>Paxbp1</i> gene in mouse T cells. In the absence of Paxbp1, naïve CD4 T cells displayed reduced surface interleukin-7 receptor levels and a decreased capacity to respond to survival signals mediated by interleukin-7. In addition, naïve CD4 T cells deficient in Paxbp1 demonstrated impaired T cell antigen receptor signalling, compromised cell cycle entry, decreased proliferation, and increased apoptosis following stimulation, all of which contributed to the reduction in the number of peripheral CD4 T cells. Therefore, our study highlights the indispensable role of Paxbp1 in maintaining peripheral CD4 T cell homeostasis.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"641-652"},"PeriodicalIF":4.9,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943645","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}

{"title":"Glycans in melanoma: Drivers of tumour progression but sweet targets to exploit for immunotherapy","authors":"Camille Niveau,&nbsp;Eleonora Sosa Cuevas,&nbsp;Philippe Saas,&nbsp;Caroline Aspord","doi":"10.1111/imm.13801","DOIUrl":"10.1111/imm.13801","url":null,"abstract":"<p>Aberrant glycosylation recently emerged as an unmissable hallmark of cancer progression in many cancers. In melanoma, there is growing evidence that the tumour ‘glycocode’ plays a major role in promoting cell proliferation, invasion, migration, but also dictates the nature of the immune infiltrate, which strongly affects immune cell function, and clinical outcome. Aberrant glycosylation patterns dismantle anti-tumour defence through interactions with lectins on immune cells, which are crucial to shape anti-tumour immunity but also to trigger immune evasion. The glycan/lectin axis represents a new immune subversion pathway that is exploited by melanoma to hijack immune cells and escape from immune control. In this review, we describe the glycosylation features of melanoma tumour cells, and further gather findings related to the role of glycosylation in melanoma tumour progression, deciphering in detail its impact on immunity. We also depict glycan-based strategies aiming at restoring a functional anti-tumour response in melanoma patients. Glycans/lectins emerge as key immune checkpoints with promising translational properties. Exploitation of these pathways could reshape potent anti-tumour immunity while impeding immunosuppressive circuits triggered by aberrant tumour glycosylation patterns, holding great promise for cancer therapy.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"33-52"},"PeriodicalIF":4.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916331","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}

{"title":"Human CD4+ iNKT cell adoptive immunotherapy induces anti-tumour responses against CD1d-negative EBV-driven B lymphoma","authors":"Dana C. Baiu,&nbsp;Akshat Sharma,&nbsp;Jennifer L. Schehr,&nbsp;Jayati Basu,&nbsp;Kelsey A. Smith,&nbsp;Makoto Ohashi,&nbsp;Eric C. Johannsen,&nbsp;Shannon C. Kenney,&nbsp;Jenny E. Gumperz","doi":"10.1111/imm.13799","DOIUrl":"10.1111/imm.13799","url":null,"abstract":"<p>Invariant natural killer T (iNKT) cells are a conserved population of innate T lymphocytes that are uniquely suitable as off-the-shelf cellular immunotherapies due to their lack of alloreactivity. Two major subpopulations of human iNKT cells have been delineated, a CD4⁻ subset that has a T_H1/cytolytic profile, and a CD4⁺ subset that appears polyfunctional and can produce both regulatory and immunostimulatory cytokines. Whether these two subsets differ in anti-tumour effects is not known. Using live cell imaging, we found that CD4⁻ iNKT cells limited growth of CD1d⁺ Epstein–Barr virus (EBV)-infected B-lymphoblastoid spheroids in vitro, whereas CD4⁺ iNKT cells showed little or no direct anti-tumour activity. However, the effects of the two subsets were reversed when we tested them as adoptive immunotherapies in vivo using a xenograft model of EBV-driven human B cell lymphoma. We found that EBV-infected B cells down-regulated CD1d in vivo, and administering CD4⁻ iNKT cells had no discernable impact on tumour mass. In contrast, xenotransplanted mice bearing lymphomas showed rapid reduction in tumour mass after administering CD4⁺ iNKT cells. Immunotherapeutic CD4⁺ iNKT cells trafficked to both spleen and tumour and were associated with subsequently enhanced responses of xenotransplanted human T cells against EBV. CD4⁺ iNKT cells also had adjuvant-like effects on monocyte-derived DCs and promoted antigen-dependent responses of human T cells in vitro. These results show that allogeneic CD4⁺ iNKT cellular immunotherapy leads to marked anti-tumour activity through indirect pathways that do not require tumour cell CD1d expression and that are associated with enhanced activity of antigen-specific T cells.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"627-640"},"PeriodicalIF":4.9,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912092","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}

{"title":"The powerful potential of amino acid menthyl esters for anti-inflammatory and anti-obesity therapies","authors":"Seidai Takasawa,&nbsp;Kosuke Kimura,&nbsp;Masato Miyanaga,&nbsp;Takuya Uemura,&nbsp;Masakazu Hachisu,&nbsp;Shinichi Miyagawa,&nbsp;Abdelaziz Ramadan,&nbsp;Satoru Sukegawa,&nbsp;Masaki Kobayashi,&nbsp;Seisuke Kimura,&nbsp;Kenji Matsui,&nbsp;Mitsunori Shiroishi,&nbsp;Kaori Terashita,&nbsp;Chiharu Nishiyama,&nbsp;Takuya Yashiro,&nbsp;Kazuki Nagata,&nbsp;Yoshikazu Higami,&nbsp;Gen-ichiro Arimura","doi":"10.1111/imm.13798","DOIUrl":"10.1111/imm.13798","url":null,"abstract":"<p>Our newly developed menthyl esters of valine and isoleucine exhibit anti-inflammatory properties beyond those of the well-known menthol in macrophages stimulated by lipopolysaccharide (LPS) and in a mouse model of colitis induced by sodium dextran sulfate. Unlike menthol, which acts primarily through the cold-sensitive TRPM8 channel, these menthyl esters displayed unique mechanisms that operate independently of this receptor. They readily penetrated target cells and efficiently suppressed LPS-stimulated tumour necrosis factor-alpha (<i>Tnf)</i> expression mediated by liver X receptor (LXR), a key nuclear receptor that regulates intracellular cholesterol and lipid balance. The menthyl esters showed affinity for LXR and enhanced the transcriptional activity through their non-competitive and potentially synergistic agonistic effect. This effect can be attributed to the crucial involvement of SCD1, an enzyme regulated by LXR, which is central to lipid metabolism and plays a key role in the anti-inflammatory response. In addition, we discovered that the menthyl esters showed remarkable efficacy in suppressing adipogenesis in 3T3-L1 adipocytes at the mitotic clonal expansion stage in an LXR-independent manner as well as in mice subjected to diet-induced obesity. These multiple capabilities of our compounds establish them as formidable allies in the fight against inflammation and obesity, paving the way for a range of potential therapeutic applications.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 1","pages":"76-92"},"PeriodicalIF":4.9,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891505","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}

{"title":"FG-4592 protected haematopoietic system from ionising radiation in mice","authors":"Yuedong Wang,&nbsp;Ying Cheng,&nbsp;Pei Zhang,&nbsp;Daqian Huang,&nbsp;Xuanlu Zhai,&nbsp;Zhenlan Feng,&nbsp;Duo Fang,&nbsp;Cong Liu,&nbsp;Jicong Du,&nbsp;Jianming Cai","doi":"10.1111/imm.13797","DOIUrl":"10.1111/imm.13797","url":null,"abstract":"<p>Ionising radiation exposure can lead to acute haematopoietic radiation syndrome. Despite significant advancements in the field of radioprotection, no drugs with high efficacy and low toxicity have yet been approved by the Food and Drug Administration. FG-4592, as a proline hydroxylase inhibitor, may play an important role in radioprotection of the haematopoietic system. Mice were peritoneal injected with FG-4592 or normal saline. After irradiation, the survival time, body weight, peripheral blood cell and bone marrow cell (BMC) count, cell apoptosis, pathology were analysed and RNA-sequence technique (RNA-Seq) was conducted to explore the mechanism of FG-4592 in the haematopoietic system. Our results indicated that FG-4592 improved the survival rate and weight of irradiated mice and protected the spleen, thymus and bone marrow from IR-induced injury. The number of BMCs was increased and protected against IR-induced apoptosis. FG-4592 also promoted the recovery of the blood system and erythroid differentiation. The results of RNA-Seq and Western blot showed that the NF-κB signalling pathway and hypoxia-inducible factor-1 (HIF-1) signalling pathway were upregulated by FG-4592. Meanwhile, RT-PCR results showed that FG-4592 could promote inflammatory response significantly. FG-4592 exhibited radioprotective effects in the haematopoietic system by promoting inflammatory response and targeting the NF-κB, HIF signalling pathway.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"614-626"},"PeriodicalIF":4.9,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841975","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}

{"title":"Oligodeoxynucleotides containing CpG motifs (CpG-ODN) restores immune regulatory functions of airway macrophages of patients with asthma","authors":"Huanping Zhang,&nbsp;Lihuan Wang,&nbsp;Aizhi Zhang,&nbsp;Xiangyu Wang,&nbsp;Yun Liao,&nbsp;Xiaoxue Chen,&nbsp;Xuejie Xu,&nbsp;Litao Yang,&nbsp;Yu Liu,&nbsp;Aifa Tang,&nbsp;Pingchang Yang","doi":"10.1111/imm.13792","DOIUrl":"10.1111/imm.13792","url":null,"abstract":"<p>Allergic asthma is characterized by the polarization of Th2 cells and impaired immune regulation. Macrophages occupy the largest proportion of airway immune cells. This study aims to discover the mechanism that hinders the immune regulatory functions of airway macrophages. In this study, macrophages were isolated from cells in bronchoalveolar lavage fluids (BALF) collected from asthma patients and normal control (NC) subjects. The results indicated that macrophages occupied the largest portion of the cellular components in BALF. The frequency of IL-10⁺ macrophage was significantly lower in asthma patients than in NC subjects. The expression of IL-10 in macrophages of BALF was associated with the levels of asthma-related parameters. The immune-suppressive functions of BALF M0 cells were defective in asthma patients. The inducibility of IL-10 expression was impaired in BALF macrophages of asthma patients, which could be restored by exposing to CpG. In conclusion, the induction of IL-10 in macrophages of BALF in asthma patients was impaired, and it could be restored by exposure to CpG.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"588-599"},"PeriodicalIF":4.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626189","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}

{"title":"Unravelling CD4+ T cell diversity and tissue adaptation of Tregs in abdominal aortic aneurysms through single-cell sequencing","authors":"Luna Zhai,&nbsp;Wangling Hu,&nbsp;Jingyong Li,&nbsp;Dan Li,&nbsp;Ni Xia,&nbsp;Tingting Tang,&nbsp;Shaofang Nie,&nbsp;Min Zhang,&nbsp;Jiao Jiao,&nbsp;Bingjie Lv,&nbsp;Fen Yang,&nbsp;Yuzhi Lu,&nbsp;Lingfeng Zha,&nbsp;Muyang Gu,&nbsp;Xiajun Hu,&nbsp;Shuang Wen,&nbsp;Desheng Hu,&nbsp;Li Zhang,&nbsp;Weimin Wang,&nbsp;Xiang Cheng","doi":"10.1111/imm.13796","DOIUrl":"10.1111/imm.13796","url":null,"abstract":"<p>Immune cell infiltration is a significant pathological process in abdominal aortic aneurysms (AAA). T cells, particularly CD4⁺ T cells, are essential immune cells responsible for substantial infiltration of the aorta. Regulatory T cells (Tregs) in AAA have been identified as tissue-specific; however, the time, location, and mechanism of acquiring the tissue-specific phenotype are still unknown. Using single-cell RNA sequencing (scRNA-seq) on CD4⁺ T cells from the AAA aorta and spleen, we discovered heterogeneity among CD4⁺ T cells and identified activated, proliferating and developed aorta Tregs. These Tregs originate in the peripheral tissues and acquire the tissue-specific phenotype in the aorta. The identification of precursors for Tregs in AAA provides new insight into the pathogenesis of AAA.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 4","pages":"600-613"},"PeriodicalIF":4.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626072","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}