International immunology最新文献_第6页

Functional diversity and tissue-specific regulation of Group 2 innate lymphoid cells in barrier immunity. 第2组先天淋巴样细胞在屏障免疫中的功能多样性和组织特异性调控。

IF 3.4 4区医学

International immunology Pub Date : 2026-04-01 DOI: 10.1093/intimm/dxaf062

Mitsuki Ito, Yunzi Yan, Naoko Satoh-Takayama

{"title":"Functional diversity and tissue-specific regulation of Group 2 innate lymphoid cells in barrier immunity.","authors":"Mitsuki Ito, Yunzi Yan, Naoko Satoh-Takayama","doi":"10.1093/intimm/dxaf062","DOIUrl":"10.1093/intimm/dxaf062","url":null,"abstract":"Group 2 innate lymphoid cells (ILC2s) contribute to the maintenance of tissue homeostasis by promoting tissue repair and regulating immune responses. However, excessive or prolonged activation of ILC2s can induce chronic inflammation and tissue fibrosis, thereby contributing to disease exacerbation and progression. Recent studies have revealed that the mechanisms underlying ILC2 activation and their effector functions vary considerably across different tissues. Therefore, understanding the tissue-specific regulation and function of ILC2s is essential for elucidating their roles in both physiological and pathological contexts. Here, we highlight the distinct functional roles of ILC2s in the stomach, intestine, lung, and skin. We examine the differences in activation cues and key effector cytokines produced by ILC2s, illustrating how these cells adapt to the unique immune environments of each tissue. Furthermore, although ILC2s were once thought to function independently of the microbiota, recent findings suggest that microbial communities may influence their activation and function. We also discuss the emerging roles of ILC2s in various diseases, including allergies, inflammatory disorders, and cancer, emphasizing their dual roles in both host defense and disease exacerbation. Gaining a deeper understanding of the distinct functional roles of ILC2s across different tissues will enhance our insight into their involvement in disease pathogenesis and may open new avenues for targeted therapeutic strategies that modulate ILC2 responses.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"210-221"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250939","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

KRAS mutations disrupt interactions between CD8+ T cells and antigen-presenting cells in the tumor microenvironment of biliary tract cancer. KRAS突变破坏了胆道癌肿瘤微环境中CD8+ T细胞和抗原提呈细胞之间的相互作用。

IF 3.4 4区医学

International immunology Pub Date : 2026-04-01 DOI: 10.1093/intimm/dxaf065

Fumihiro Terasaki, Shogo Kumagai, Akito Fukuda, Yosuke Tanaka, Takuma Irie, Sachiko Ito, Mihoko Yamada, Shunsuke Onoe, Takashi Mizuno, Toshio Kokuryo, Shohei Koyama, Kennosuke Karube, Hiroyoshi Nishikawa, Tomoki Ebata

{"title":"KRAS mutations disrupt interactions between CD8+ T cells and antigen-presenting cells in the tumor microenvironment of biliary tract cancer.","authors":"Fumihiro Terasaki, Shogo Kumagai, Akito Fukuda, Yosuke Tanaka, Takuma Irie, Sachiko Ito, Mihoko Yamada, Shunsuke Onoe, Takashi Mizuno, Toshio Kokuryo, Shohei Koyama, Kennosuke Karube, Hiroyoshi Nishikawa, Tomoki Ebata","doi":"10.1093/intimm/dxaf065","DOIUrl":"10.1093/intimm/dxaf065","url":null,"abstract":"Biliary tract cancer (BTC) exhibits a poor prognosis and limited responses to current therapeutic strategies. While surgical resection followed by adjuvant S-1 therapy is the standard curative treatment for BTC, long-term postoperative remission is hardly achieved. Therefore, more effective perioperative strategies are urgently needed. Here, we show that an immune-cold tumor microenvironment (TME) in KRAS-mutated BTC correlated with resistance to postoperative adjuvant S-1 therapy. Surgically resected tumor specimens were collected from 31 BTC patients who received adjuvant S-1 therapy after surgery and were subjected to integrated immunogenomic analysis, including multiplexed immunohistochemistry staining and whole-exome sequencing. The analysis revealed a strong correlation between limited CD8⁺ T cell and antigen-presenting cell (APC) infiltration into the TME and KRAS mutations in BTC. In addition, the distances between tumor cells and APCs, as well as between APCs and CD8⁺ T cells, were significantly greater in the TME of KRAS-mutated BTC than in that of KRAS wild-type BTC. These findings indicate that interactions between effector T cells and APCs were impaired in the TME of KRAS-mutated BTC, thereby disrupting antitumor immune responses. Furthermore, wild-type KRAS and abundant CD8⁺ T cells and APCs correlated with a favorable prognosis following adjuvant S-1 therapy for BTC. Altogether, we propose a novel immunogenomic-based biomarker for optimizing perioperative chemotherapy for BTC.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"236-250"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438075","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

Alcaligenes lipid A as a sublingual adjuvant to augment protective immune responses in the respiratory and gastrointestinal tracts. Alcaligenes脂质A作为舌下佐剂增强呼吸道和胃肠道的保护性免疫反应。

IF 3.4 4区医学

International immunology Pub Date : 2026-04-01 DOI: 10.1093/intimm/dxaf066

Ken Yoshii, Zilai Liu, Atsushi Shimoyama, Yuki Hirayama, Keigo Iemitsu, Eri Node, Koji Hosomi, Hiroshi Kiyono, Koichi Fukase, Jun Kunisawa

{"title":"Alcaligenes lipid A as a sublingual adjuvant to augment protective immune responses in the respiratory and gastrointestinal tracts.","authors":"Ken Yoshii, Zilai Liu, Atsushi Shimoyama, Yuki Hirayama, Keigo Iemitsu, Eri Node, Koji Hosomi, Hiroshi Kiyono, Koichi Fukase, Jun Kunisawa","doi":"10.1093/intimm/dxaf066","DOIUrl":"10.1093/intimm/dxaf066","url":null,"abstract":"We previously identified Alcaligenes as symbiotic bacteria residing within Peyer's patches and demonstrated that their primary components, lipopolysaccharides, and their active center, lipid A, are excellent adjuvants for mucosal vaccination. Here, we evaluated the effectiveness of Alcaligenes-derived lipid A as an adjuvant for sublingual immunization, a novel vaccination route. Mice sublingually immunized with Alcaligenes lipid A and ovalbumin (OVA) showed enhanced production of OVA-specific IgA in both the respiratory and gastrointestinal tracts. In addition, increased serum levels of OVA-specific and IgG antibodies were elicited through germinal center reactions in the draining lymph nodes without excessive inflammation at the administration sites. These results demonstrated superior efficacy not previously achieved through other routes of administration (e.g. intranasal, subcutaneous, intramuscular administration) or by existing adjuvants (e.g. CpG-ODN). In addition, sublingual immunization with cholera toxin B subunit (CTB) and lipid A led to an elevated CTB-specific IgG response in the systemic compartment and an elevated IgA response in the intestinal tract, effectively suppressing the diarrhea induced by oral challenge with cholera toxin. Furthermore, immunization with pneumococcal surface protein A (PspA) plus Alcaligenes lipid A elicited strong PspA-specific CD4+ T cell proliferation and Th17 responses, as well as IgA and IgG responses, in both the respiratory tract and the systemic compartment. These effects enhanced pneumococcal clearance in the lungs and subsequent protection against Streptococcus pneumoniae infection. Together, our findings suggest that Alcaligenes-derived lipid A is a potent sublingual vaccine adjuvant with potential efficacy against both respiratory and intestinal infectious diseases.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"264-277"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488596","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

Interaction between neurons and microglia in healthy and disease states. 健康和疾病状态下神经元和小胶质细胞之间的相互作用。

IF 3.4 4区医学

International immunology Pub Date : 2026-03-09 DOI: 10.1093/intimm/dxaf057

Ayaka Nakamura, Takashi Shichita

{"title":"Interaction between neurons and microglia in healthy and disease states.","authors":"Ayaka Nakamura, Takashi Shichita","doi":"10.1093/intimm/dxaf057","DOIUrl":"10.1093/intimm/dxaf057","url":null,"abstract":"Interactions between neurons and microglia are essential for various brain functions under both healthy and pathological states. Microglia have classical functions as immune cells, causing cerebral inflammation, whereas their reparative roles after acute cerebral inflammation have recently attracted attention. In the healthy brain state, microglia contribute to homeostasis and brain tissue development. Microglia regulate neuronal activity by responding to molecules derived from neurons and eliminating excess synapses to achieve normal brain development and maintain a homeostatic brain environment. Microglia are also involved in neuronal information processing, such as learning and memory, by modulating synaptic remodeling and neurogenesis. In contrast, aging alters brain homeostasis and increases vulnerability to neurodegenerative pathologies through changes in interactions between neurons and microglia. Microglia exert diverse functions in neurological and psychiatric diseases. Microglia are responsible for rapid inflammatory responses by receiving abnormal signals from injured brain cells. Excess neuroinflammation mediated by disease-associated microglia exacerbates the pathology of central nervous system (CNS) diseases. Recent studies have also revealed the roles of microglia in improving pathologies through the phagocytosis of neurotoxic proteins and damaged or excess synapses. This review highlights the interaction between neurons and microglia in both healthy and pathological brain states. Understanding these interactions could lead to the development of therapeutic strategies by regulating the pathologies underlying various CNS disorders.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"154-162"},"PeriodicalIF":3.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148971","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

Neuroprotective crosstalk from vitamin B12 and sphingolipid signaling pathways in therapy for multiple sclerosis. 来自维生素B12和鞘脂信号通路的神经保护串扰在多发性硬化治疗中的作用。

IF 3.4 4区医学

International immunology Pub Date : 2026-03-09 DOI: 10.1093/intimm/dxaf058

Yasuyuki Kihara, Jerold Chun

{"title":"Neuroprotective crosstalk from vitamin B12 and sphingolipid signaling pathways in therapy for multiple sclerosis.","authors":"Yasuyuki Kihara, Jerold Chun","doi":"10.1093/intimm/dxaf058","DOIUrl":"10.1093/intimm/dxaf058","url":null,"abstract":"Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) characterized by neuroinflammation, demyelination, and neurodegeneration. Among disease-modifying therapies, sphingosine 1-phosphate (S1P) receptor (S1PR) modulators such as fingolimod, also known as FTY720, have been shown to exert therapeutic effects through direct CNS actions at S1PRs (e.g. S1P1) expressed by astrocytes, beyond the originally proposed mechanism action of lymphocyte sequestration. This review highlights the emerging evidence linking S1P signaling to the vitamin B12 pathway, including transcobalamin 2 (TCN2) and CD320. Functional interaction between S1P1 signaling and CD320 expression was discovered by examining gene expression changes in immediate-early astrocytes (ieAstrocytes), the primary CNS cell type activated in response to neuroinflammatory stimuli. This discovery led to the identification of the physical interaction between fingolimod/sphingosine and TCN2 and the potentiation of CD320 internalization by this complex. These findings underscore the importance of CNS vitamin B12 levels in MS and likely other neurological diseases and help to explain the long-appreciated shared neurological symptoms between vitamin B12 deficiency and MS. Future research should investigate therapeutic strategies targeting the crosstalk between the sphingolipid and vitamin B12 pathways to enhance CNS vitamin B12 availability, which can promote neuroprotection in MS and related diseases.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"163-171"},"PeriodicalIF":3.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13016721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137398","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

Role of Group 2 innate lymphoid cells in intranasal sensitization-induced allergic rhinitis in mice. 2组先天淋巴样细胞在小鼠鼻内致敏性变应性鼻炎中的作用。

IF 3.4 4区医学

International immunology Pub Date : 2026-03-09 DOI: 10.1093/intimm/dxaf060

Yukinori Kato, Tetsuji Takabayashi, Anna Shimizu, Ayako Maegawa, Eiichi Kato, Naoto Adachi, Keisuke Koyama, Kyoko Saito, Kanako Yoshida, Masanori Kidoguchi, Taiyo Morikawa, Yoshimasa Imoto, Masafumi Sakashita, Mamoru Ito, Masato Kubo, Shigeharu Fujieda

{"title":"Role of Group 2 innate lymphoid cells in intranasal sensitization-induced allergic rhinitis in mice.","authors":"Yukinori Kato, Tetsuji Takabayashi, Anna Shimizu, Ayako Maegawa, Eiichi Kato, Naoto Adachi, Keisuke Koyama, Kyoko Saito, Kanako Yoshida, Masanori Kidoguchi, Taiyo Morikawa, Yoshimasa Imoto, Masafumi Sakashita, Mamoru Ito, Masato Kubo, Shigeharu Fujieda","doi":"10.1093/intimm/dxaf060","DOIUrl":"10.1093/intimm/dxaf060","url":null,"abstract":"Cells of the innate immune system, specifically Group 2 innate lymphoid cells (ILC2s), play an important role in Type 2 inflammation. However, their involvement in allergic rhinitis remains unclear. Thus, in this study, we aimed to clarify the role of ILC2s and acquired immune responses in the onset of allergic rhinitis induced via intranasal mucosal sensitization with antigens in mice. Naive mice were intranasally administered antigens in the short term (4 consecutive days) or long term (21 consecutive days). The number of sneezes, serum-specific immunoglobulin E (IgE) levels, and eosinophil infiltration in the nasal mucosa were subsequently assessed. Short-term intranasal antigen administration to naive mice induced eosinophilic inflammation of the nasal mucosa in an acquired immune-independent and protease- and ILC2-dependent manner. Antigen-independent sneezing was caused by a calcium influx response via transient receptor potential vanilloid channels. In contrast, long-term intranasal mucosal sensitization with antigens led to the onset of allergic rhinitis. Furthermore, increased serum-specific IgE levels and sneezing frequency, as well as significant eosinophilic infiltration, were observed in the nasal mucosa. ILC2s in the nasal mucosa did not proliferate upon short-term stimulation with antigens but proliferated upon long-term stimulation, facilitating acquired immunity and allergic rhinitis onset. Our findings demonstrated that allergic inflammation is induced by the protease/IL-33/ILC2/IL-5 axis during the initiator phase. Acquired immunity induced by long-term sensitization and innate immunity facilitated by short-term sensitization together induce significant allergic inflammation and allergic rhinitis onset.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"172-184"},"PeriodicalIF":3.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250950","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

mTORC1-independent IgA production: a unique pathway for gut immune homeostasis. mtorc1独立的IgA生产：肠道免疫稳态的独特途径。

IF 3.4 4区医学

International immunology Pub Date : 2026-03-09 DOI: 10.1093/intimm/dxaf063

Masashi Ohtani, Hideki Fujii, Takashi Watanabe, Osamu Ohara, Mikako Maruya, Sidonia Fagarasan, Takayuki Hoshii, Atsushi Hirao, Shigeo Koyasu, Masato Kubo, Satoshi Matsuda

{"title":"mTORC1-independent IgA production: a unique pathway for gut immune homeostasis.","authors":"Masashi Ohtani, Hideki Fujii, Takashi Watanabe, Osamu Ohara, Mikako Maruya, Sidonia Fagarasan, Takayuki Hoshii, Atsushi Hirao, Shigeo Koyasu, Masato Kubo, Satoshi Matsuda","doi":"10.1093/intimm/dxaf063","DOIUrl":"10.1093/intimm/dxaf063","url":null,"abstract":"The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) regulates various cellular processes, including immune responses. Previous studies have demonstrated that mTORC1 plays a crucial role in B cell differentiation and the production of IgM and IgG antibodies in response to foreign antigens. However, its role in steady-state antibody production remains poorly understood. In this study, we found that RaptorB-/- mice, which have a B cell-specific deletion of Raptor (an essential component of mTORC1), retained gut-associated IgA production. Conversely, IgM and IgG subclasses were virtually absent due to the loss of peripheral IgM+ mature B cells. We also found that IgA-producing cells were driven by the gut microbiota and were primarily localized in the intestinal lamina propria of RaptorB-/- mice. Consistently, IgA produced in RaptorB-/- mice was functional in its ability to bind gut bacteria and contributed to maintaining gut microbiota α-diversity, although its repertoire was restricted compared with that of control mice. Our findings demonstrated a distinct population of IgA-producing cells that develop independently of mTORC1 and contribute to gut homeostasis, thereby distinguishing them from conventional IgM- and IgG-producing cells.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"185-196"},"PeriodicalIF":3.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344900","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

TACI is required for the survival of short- and long-lived plasma cells. TACI是短寿命和长寿命浆细胞存活所必需的。

IF 3.4 4区医学

International immunology Pub Date : 2026-03-09 DOI: 10.1093/intimm/dxaf067

Kenji Funakoshi, Takuya Koike, Wataru Ise, Yuki Tai, Masashi Narazaki, Atsushi Kumanogoh, Takeshi Inoue, Tomohiro Kurosaki

{"title":"TACI is required for the survival of short- and long-lived plasma cells.","authors":"Kenji Funakoshi, Takuya Koike, Wataru Ise, Yuki Tai, Masashi Narazaki, Atsushi Kumanogoh, Takeshi Inoue, Tomohiro Kurosaki","doi":"10.1093/intimm/dxaf067","DOIUrl":"10.1093/intimm/dxaf067","url":null,"abstract":"In a typical immune response, naïve B cells are activated, differentiated into short-lived plasma cells (SLPCs), and then matured into long-lived plasma cells (LLPCs) in the bone marrow. Among three TNF family receptors (BAFF-R, TACI, and BCMA), BAFF-R and BCMA are known to be crucial for the maintenance of naïve B cells and bone marrow LLPCs, respectively. In contrast, the function of TACI remains unclear, as analysis of global TACI knockout mice suggests the existence of two opposing roles in B and plasma cells. Here, to define the role of TACI during T cell-dependent (TD) immune responses in a B and plasma cell-intrinsic manner, we utilized adoptive transfer experiments employing B cells with a conditional TACI knockout. We show that B cell activation is apparently normal in the absence of TACI, while it is crucial for the expansion of IgM+ and IgG1+ SLPCs and maintenance of their resultant bone marrow LLPCs. Hence, our data suggest that the hyper-B cell activation seen in global TACI knockout mice could be due to an indirect control of BAFF levels or B cell extrinsic anomalies.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"197-206"},"PeriodicalIF":3.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488694","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

The chitosan nanoparticle-based adjuvant CH-100 orchestrates multifaceted innate immune activation via STING-dependent and -independent pathways. 壳聚糖纳米颗粒佐剂CH-100通过sting依赖性和非依赖性途径协调多方面的先天免疫激活。

IF 3.4 4区医学

International immunology Pub Date : 2026-02-09 DOI: 10.1093/intimm/dxaf054

Eri Nagai, Daisuke Ori, Norisuke Kano, Moe Ikegawa, Kouji Kobiyama, Ken J Ishii, Takumi Kawasaki, Taro Kawai

{"title":"The chitosan nanoparticle-based adjuvant CH-100 orchestrates multifaceted innate immune activation via STING-dependent and -independent pathways.","authors":"Eri Nagai, Daisuke Ori, Norisuke Kano, Moe Ikegawa, Kouji Kobiyama, Ken J Ishii, Takumi Kawasaki, Taro Kawai","doi":"10.1093/intimm/dxaf054","DOIUrl":"10.1093/intimm/dxaf054","url":null,"abstract":"Adjuvants enhance vaccine efficacy by activating innate immunity; yet, the mechanisms of nanoparticle-based adjuvants remain incompletely defined. Here, we characterize CH-100, a chitosan nanoparticle adjuvant, and its capacity to coordinate dendritic cell (DC) activation and promote adaptive immune responses. CH-100 enhances antigen uptake, upregulates co-stimulatory molecules, and elicits antigen-specific antibody and cytotoxic T lymphocytes (CTL) responses. Mechanistically, CH-100 induces mitochondrial reactive oxygen species (ROS), leading to NLRP3 inflammasome activation, although NLRP3 is not essential for the observed adaptive responses. In parallel, CH-100 triggers the STING-IRF3 pathway to induce type I interferons; STING-deficiency partially diminishes antibody and CTL responses, suggesting involvement of additional signaling. Transcriptomic analysis reveals STING-independent upregulation of genes related to Th17 differentiation, accompanied by activation of TBK1, NF-κB, and p38 pathways in DCs, ultimately promoting Th17-skewed immunity. These findings demonstrate how CH-100 engages both STING-dependent and -independent innate pathways to shape adaptive immunity, offering mechanistic insights into chitosan-based adjuvants for future vaccine development.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"118-133"},"PeriodicalIF":3.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091609","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

Direct analysis of hepatic stellate cells with flow cytometry in specimens derived from the human liver. 用流式细胞术直接分析人肝脏标本中的肝星状细胞。

IF 3.4 4区医学

International immunology Pub Date : 2026-02-09 DOI: 10.1093/intimm/dxaf055

Toshiaki Bando, Hirotaka Sato, Shunsuke Uno, Hajime Morita, Lynn Zreka, Shuhe Ma, Mouna Khan, Daichi Akuzawa, Yuki Masuo, Joey Matsuyama, Ryo Nishida, Shinya Okumura, Etsuro Hatano, Takashi Ito, Hideki Ueno

{"title":"Direct analysis of hepatic stellate cells with flow cytometry in specimens derived from the human liver.","authors":"Toshiaki Bando, Hirotaka Sato, Shunsuke Uno, Hajime Morita, Lynn Zreka, Shuhe Ma, Mouna Khan, Daichi Akuzawa, Yuki Masuo, Joey Matsuyama, Ryo Nishida, Shinya Okumura, Etsuro Hatano, Takashi Ito, Hideki Ueno","doi":"10.1093/intimm/dxaf055","DOIUrl":"10.1093/intimm/dxaf055","url":null,"abstract":"Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis. However, the methodology to directly assess the biology of primary HSCs in human liver specimens is yet to be established. In this study, we aimed to establish a robust methodology to analyse primary HSCs in human liver specimens with flow cytometry (FCM). We first applied FCM to HSCs directly isolated from liver tissues with Nycodenz density gradients. Then, we analysed HSCs in frozen/thawed liver perfusate samples and liver tissues. We also compared the phenotype of HSCs in primary biliary cholangitis (PBC) and those in healthy counterparts. We found that HSCs were substantially smaller and less dense than normal lymphocytes in the FCM analysis. By carefully defining the FCM gating strategy, we were able to establish the approach to analyse both quiescent HSCs (qHSCs) and activated HSCs (aHSCs) in human liver specimens. Importantly, we found that co-expression of CD14 and CD56 within CD45 non-immune cells permits the detection of qHSCs, whereas CD68 and CD40 within CD45 non-immune cells were valuable for assessing aHSCs. Furthermore, we found that aHSCs in PBC upregulated the expression of multiple markers associated with antigen-presentation capacity. Our established approach with FCM will be valuable for the direct analysis of qHSCs and aHSCs with FCM in various human liver specimens. Our FCM analysis of aHSCs in PBC suggested their involvement in the local immune responses.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"134-149"},"PeriodicalIF":3.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091642","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