Article
Biochemistry & Molecular Biology
Hung-Wen Chen, Chia- Lin, Ya-Hui Chuang
Summary: IL-30 treatment reduces activated CD4(+) T cells and regulatory T cells, but does not suppress liver inflammation in the murine model of PBC.
Article
Immunology
Chia- Lin, Yu-Wen Wang, Chih-Yu Liu, Hung-Wen Chen, Pi-Hui Liang, Ya-Hui Chuang
Summary: In this study, the researchers used a mouse model to investigate the functionality of regulatory T cells (Tregs) in primary biliary cholangitis (PBC). They found that Tregs in the inflamed liver of PBC patients were insufficient in suppressing pathological immune responses. Additionally, CD8 T cells were identified as the primary effector cells in PBC.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Julian Hercun, Mazen Noureddin, Nabil Noureddin, Jason Eccleston, Daniel Woolridge, T. Jake Liang, Michele Tana, David E. Kleiner, Gracia Viana Rodriguez, Christopher Koh, Jay H. Hoofnagle, Theo Heller
Summary: This study evaluated the involvement of bile duct and disease progression in patients with primary biliary cholangitis (PBC) and found that bile duct injury does not follow the same course as fibrosis, and certain indicators are associated with ductopenia progression.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Immunology
Chunhui She, Yifei Yang, Bo Zang, Yuan Yao, Qixuan Liu, Patrick S. C. Leung, Bin Liu
Summary: This study found that the expression levels of LncRNA XIST in NK cells and CD4+ T cells were significantly higher in PBC patients and primarily located in the nucleus. LncRNA XIST could promote the proliferation of naive CD4+ T cells and decrease the expression of related cytokines in naive CD4+ T cells when co-cultured with bile duct epithelial cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Sha Chen, Tingting Lv, Guangyong Sun, Shuxiang Li, Weijia Duan, Chunpan Zhang, Hua Jin, Dan Tian, Mingyang Li, Shan Shan, Hong Ma, Xiaojuan Ou, Hong You, Dong Zhang, Jidong Jia
Summary: This study found that the number of circulating TCRγδ low-expressing subset cells was significantly decreased in patients with primary biliary cholangitis (PBC). These cells may migrate to the liver via the CXCR6-CXCL16 axis and be involved in the pathogenesis of PBC by increasing granzyme B (GZMB) production.
HEPATOLOGY INTERNATIONAL
(2022)
Review
Immunology
Jason Cheung, Beata Zahorowska, Michael Suranyi, Jeffrey K. W. Wong, Jason Diep, Stephen T. T. Spicer, Nirupama D. D. Verma, Suzanne J. Hodgkinson, Bruce M. M. Hall
Summary: The immune response to an allograft can activate lymphocytes that cause rejection. The activation of T regulatory cells can reduce allograft rejection and induce immune tolerance. Activated T regulatory cells can be distinguished by various markers. A more detailed characterization of these cells may help reduce non-specific immunosuppression.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Xi Li, Yan Li, Jintao Xiao, Huiwen Wang, Yan Guo, Xiuru Mao, Pan Shi, Yanliang Hou, Xiaoxun Zhang, Nan Zhao, Minghua Zheng, Yonghong He, Jingjing Ding, Ya Tan, Min Liao, Ling Li, Ying Peng, Xuan Li, Qiong Pan, Qiaoling Xie, Qiao Li, Jianwei Li, Ying Li, Zhe Chen, Yongxiu Huang, David N. Assis, Shi-Ying Cai, James L. Boyer, Xuequan Huang, Can-E Tang, Xiaowei Liu, Shifang Peng, Jin Chai
Summary: The numbers of DUOX2(+)ACE2(+) small cholangiocytes are inversely associated with disease severity in PBC. They may be the target of pIgR-mediated humoral responses. Protecting these cells and targeting anti-pIgR autoantibodies could be valuable strategies for therapeutic interventions in PBC.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Gavin I. Ellis, Kimberly E. Coker, Delaine W. Winn, Mosha Z. Deng, Divanshu Shukla, Vijay Bhoj, Michael C. Milone, Wei Wang, Chengyang Liu, Ali Naji, Raimon Duran-Struuck, James L. Riley
Summary: This study describes a culture system that expands CAR Tregs specific for the Bw6 alloantigen, which has been proven to effectively suppress immune responses both in vitro and in vivo.
CELL REPORTS MEDICINE
(2022)
Review
Immunology
Ilse Gille, Frans H. J. Claas, Geert W. Haasnoot, Mirjam H. M. Heemskerk, Sebastiaan Heidt
Summary: Solid organ transplantation is an effective treatment for end-stage diseases, but the need for immunosuppression can lead to serious side effects. CAR Treg therapy, specifically with HLA-A2 CAR Tregs, shows potential in promoting transplantation tolerance and improving graft survival.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Brendan Reed, Frances Crawford, Ryan C. Hill, Niyun Jin, Janice White, S. Harsha Krovi, Philippa Marrack, Kirk Hansen, John W. Kappler
Summary: The identification of peptide epitopes presented by MHCII molecules that drive CD4 T cell autoimmunity, particularly in type 1 diabetes, has been a challenge. Recent insights suggest that important epitopes are actually chimeric epitopes pieced together from different peptide fragments, rather than directly processed from a protein source. This fusion process, known as transpeptidation, may occur during the catabolic turnover of pancreatic proteins, shedding light on how self-tolerance can be broken peripherally in autoimmune diseases like T1D.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Thomas W. Warnes, Stephen A. Roberts, Alexander Smith, Victor M. Cope, Patricia Vales, Raymond McMahon
Summary: This study found that measurement of baseline portal pressure is of significant prognostic value in primary biliary cholangitis, providing additional predictive information beyond Mayo score and Ludwig stage.
LIVER INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Debashis Haldar, Ashnila Janmohamed, Tim Plant, Matthew Davidson, Hannah Norman, Emily Russell, Olivia Serevina, Kenneth Chung, Kashif Qamar, Bridget Gunson, Bettina Hansen, Alex Richter, Palak J. Trivedi, Gideon M. Hirschfield
Summary: In patients with PBC, the presence of anti-gp210 autoantibodies is associated with adverse clinical manifestations, predicts treatment non-response, and independently predicts decreased transplant-free survival.
LIVER INTERNATIONAL
(2021)
Article
Gastroenterology & Hepatology
Roopa H. Nanjundappa, Urs Christen, Channakeshava S. Umeshappa
Summary: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two major autoimmune liver diseases. PBC primarily affects intrahepatic small bile duct epithelial cells in women, while PSC mainly affects medium and big bile duct epithelial cells in men. Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes and is more prevalent in PSC patients than in PBC patients. Understanding the immune surveillance mechanisms that differentiate between PBC and PSC patients is crucial for developing effective therapies and early diagnosis of CCA.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Roopa H. Nanjundappa, Urs Christen, Channakeshava S. Umeshappa
Summary: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two significant autoimmune liver diseases. PBC primarily affects small bile duct epithelial cells in women, while PSC predominantly affects medium and large intrahepatic and extrahepatic bile duct epithelial cells in men. Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes and its incidence is increasing worldwide. Although PBC patients rarely develop CCA compared to PSC patients, understanding the differences in immune surveillance mechanisms is crucial for effective diagnosis and treatment.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Nidhi Jalan-Sakrikar, Abid Anwar, Usman Yaqoob, Can Gan, Anthony B. Lagnado, Alexander Q. Wixom, Diana Jurk, Robert C. Huebert
Summary: This study investigated the mechanistic relationship between telomere damage and biliary fibrosis in primary sclerosing cholangitis (PSC). The results showed telomere attrition and reduced telomerase reverse transcriptase (TERT) expression in patients with PSC. Cellular models demonstrated that telomere dysfunction can lead to senescence and fibrosis, which can be rescued by modulating TERT levels.
Article
Chemistry, Physical
Jia-Si Wu, Jia-Xian Li, Na Shu, Qi-Jia Duan, Qi-Song Tong, Jing-Yang Zhang, Yong-Cong Huang, Si-Yu Yang, Zhi-Bin Zhao, Jin-Zhi Du
Summary: The study developed a novel polymer capable of polarizing TAMs into M1 phenotype, which efficiently loaded TLR7/8 agonist to remodel the tumor immunosuppressive microenvironment, enhancing the efficacy of cancer immunotherapy.
Article
Cell Biology
Junko Morimoto, Minoru Matsumoto, Ryuichiro Miyazawa, Hideyuki Yoshida, Koichi Tsuneyama, Mitsuru Matsumoto
Summary: This study reveals the significance of the interaction between mTECs and DCs coordinated by Aire in establishing thymic tolerance. Aire deficiency leads to abnormal expression of CTLA-4 in mTECs, which removes CD80/CD86 ligands from DCs, attenuating their ability to provide co-stimulatory signals and present self-antigens transferred from mTECs, resulting in impaired Treg production and organ-specific autoimmunity.
Article
Biochemical Research Methods
Yi-Hua Jiang, Jie Long, Zhi-Bin Zhao, Liang Li, Zhe-Xiong Lian, Zhi Liang, Jia-Rui Wu
Summary: This study uses part mutual information (PMI) to calculate gene co-expression networks of cancer mRNA transcriptome data, and compares it with the conventional Pearson correlation coefficient (PCC). The results show that PMI-based networks accurately represent the correlation patterns of biological data and are robust across different biological conditions. PMI-based networks also extract more important omics-defined gene pair relationships. Based on the PMI-recalled gene pair relationships, cancer patients can be divided into groups with significant differences in disease-specific survival.
BMC BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Takeo Minamikawa, Eiji Hase, Mayuko Ichimura-Shimizu, Yuki Morimoto, Akihiro Suzuki, Takeshi Yasui, Satoko Nakamura, Akemi Tsutsui, Koichi Takaguchi, Koichi Tsuneyama
Summary: In this study, second-harmonic generation microscopy was used to quantitatively assess the ultra-early stage of fibrosis in NAFLD patients. The results showed that SHG microscopy can effectively visualize fibrotic structures and early fibrosis in liver tissues, which is challenging to identify with conventional histopathological methods. Additionally, SHG emission directionality analysis can assess the maturation of collagen fibers in each patient.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Song-Rong Wang, Ren-Dong Hu, Min Ma, Xing You, Haiyan Cui, Yi He, Damo Xu, Zhi-Bin Zhao, Carlo Selmi, M. Eric Gershwin, Liang Li, Zhe-Xiong Lian
Summary: IL-10-producing B cells (B10) play an important role in the prevention of autoimmune and allergic responses. The activity of FoxO1 is inversely correlated with B10 cell frequency, and deficiency of FoxO1 leads to an increased frequency of B10 cells. Increased FoxO1 activity and decreased regulatory B cells are observed in asthma patients. FoxO1 negatively regulates B10 cell differentiation by inhibiting the expression of Prdm1.
MUCOSAL IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xiao-Long Jiang, Pan-Yue Luo, Yan-Ying Zhou, Zhi-Hui Luo, Yue-Jun Hao, Ming-Zhi Fan, Xiao-Han Wu, Hao Gao, Hui-Chang Bi, Zhi-Bin Zhao, Mei-Lan Lian, Zhe-Xiong Lian
Summary: This study investigated the protective effect of O. elatus on liver protection and found its potential in treating drug-induced hepatotoxicity through affecting drug metabolism and regulating lipid metabolism.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Mayuko Ichimura-Shimizu, Soichiro Ishimaru, Christine (Yee-Yan) Wai, Takeo Minamikawa, Takaaki Tsunematsu, Aiko Endo, Takumi Kojima, Minoru Matsumoto, Tomoko Kobayashi, Satoshi Sumida, Takumi Kakimoto, Yuko Miyakami, Hirohisa Ogawa, Takeshi Oya, Koichi Tsuneyama
Summary: This study generated a mouse model of shellfish allergy through epicutaneous sensitization, which can be used to explore the pathogenesis of skin sensitization. Raman microscopy may also provide valuable insights into subtle skin changes leading to sensitization.
APPLIED SCIENCES-BASEL
(2022)
Article
Biochemical Research Methods
Si-Yu Yang, Meng-Xing Huang, Yan-Xia Sun, Liang Li, Zhen-Hua Bian, Jie Long, Zhi-Bin Zhao
Summary: This 33-color panel is designed to delineate immune phenotypes of major lymphocyte subsets in murine tissues, identifying surface markers for cell activation, differentiation, and exhaustion. It avoids the need for fixation and permeabilization steps, enabling in-depth immunophenotyping of murine lymphocytes in immune and non-immune tissues.
JOURNAL OF IMMUNOLOGICAL METHODS
(2022)
Article
Oncology
Jialuo Mai, Xuefeng Hua, Zhen-Hua Bian, Yu Xia, Zhi-Bin Zhao, Minqiang Lu
Summary: This study analyzed the expression profiles of hepatocellular carcinoma (HCC) and identified the proportion profile of immune cells in HCC using the CIBERSORTx software. The study found that seven immune cell types were related to the overall survival of HCC patients and identified numerous differentially expressed immune-related genes. The genes were primarily involved in nucleic acid processing and metabolism. Additionally, 14 genes were identified as common candidates related to immune cells and overall survival.
TRANSLATIONAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Wenhua Shao, Orgil Jargalsaikhan, Mayuko Ichimura-Shimizu, Qinyi Cai, Hirohisa Ogawa, Yuko Miyakami, Kengo Atsumi, Mitsuru Tomita, Mitsuko Sutoh, Shunji Toyohara, Ryoji Hokao, Yasusei Kudo, Takeshi Oya, Koichi Tsuneyama
Summary: The GS-negative tumors of TSOD mice exhibit characteristics similar to various subtypes of human hepatocellular adenoma (HCA), suggesting that TSOD mice may share similar mechanisms of HCA development as in humans.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yuki Tada, Kaichi Kasai, Nana Makiuchi, Naoya Igarashi, Koudai Kani, Shun Takano, Hiroe Honda, Tsutomu Yanagibashi, Yasuharu Watanabe, Fumitake Usui-Kawanishi, Yukihiro Furusawa, Mayuko Ichimura-Shimizu, Yoshiaki Tabuchi, Kiyoshi Takatsu, Koichi Tsuneyama, Yoshinori Nagai
Summary: Macrophages play a critical role in the development of non-alcoholic steatohepatitis (NASH), but it is unclear which macrophage subset is specifically involved in inflammation and fibrosis. In this study, we found that in TSNO mice with advanced liver fibrosis resembling human NASH, recruited macrophages were more abundant than Kupffer cells (KCs) and formed hepatic crown-like structures (hCLS). The recruited macrophages consisted of CD11c(+)/Ly6C(-) and CD11c(-)/Ly6C(+) subsets, with CD11c(+)/Ly6C(-) cells promoting liver fibrosis and hepatic stellate cell (HSC) activation, while CD11c(-)/Ly6C(+) cells exhibited an anti-inflammatory role and promoted tissue repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kaichi Kasai, Naoya Igarashi, Yuki Tada, Koudai Kani, Shun Takano, Tsutomu Yanagibashi, Fumitake Usui-Kawanishi, Shiho Fujisaka, Shiro Watanabe, Mayuko Ichimura-Shimizu, Kiyoshi Takatsu, Kazuyuki Tobe, Koichi Tsuneyama, Yukihiro Furusawa, Yoshinori Nagai
Summary: The gut microbiota plays a potential role in the development of non-alcoholic fatty liver disease. Antibiotic treatments in non-obese mice fed a high-fat/cholesterol/cholate-based diet exacerbated liver damage, steatohepatitis, and fibrosis. This effect was attributed to changes in gut microbiota, particularly an increase in Gram-positive organisms, and the modulation of bile acid levels and composition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Madi Sun, Peiyu Chen, Kai Xiao, Xiang Zhu, Zhibin Zhao, Chenyang Guo, Xuan He, Tongfei Shi, Qingguo Zhong, Yong Jia, Yu Tao, Mingqiang Li, Kam W. Leong, Dan Shao
Summary: This study finds that the temporal pattern of circulating cell-free DNA (cfDNA) is strongly associated with damage and inflammation parameters in APAP-induced liver injury (AILI). CfDNA is comparable to ALT in predicting mortality and outperforms ALT when combined with ALT in AILI. Depleting cfDNA or neutrophils alleviates liver damage, while adding cfDNA or adoptive transfer of neutrophils exacerbates the damage. The combination of DNase I and N-acetylcysteine significantly attenuates AILI. This study establishes that cfDNA is a mechanistic biomarker to predict mortality in AILI mice. The combination of scavenging cfDNA and reducing oxidative damage provides a promising treatment for AILI.
Review
Allergy
Zhi-Bin Zhao, Zhen-Hua Bian, Zhang-Mei Lin, Shu-Fan Wu, Jie Long, Yang Cui, Yang Li, Wende Li, Er-Wei Sun, Zhe-Xiong Lian, Yi He
Summary: Our study characterized the immune landscape of Ax-SpA patients before and after anti-TNF alpha treatment at the single-cell level. We found an increase in peripheral granulocytes and monocytes in Ax-SpA patients, and identified a more functional subtype of regulatory T cells in synovial fluid after treatment. Additionally, we observed a cluster of inflammatory monocyte subset with stronger inflammatory and chemotactic characteristics.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mayuko Ichimura-Shimizu, Shiro Watanabe, Yuka Kashirajima, Ami Nagatomo, Hitomi Wada, Koichi Tsuneyama, Katsuhisa Omagari
Summary: This study demonstrates the direct impact of dietary cholic acid (CA) on the progression of nonalcoholic steatohepatitis (NASH) induced by a high-fat and high-cholesterol diet. Adding CA to the diet exacerbates hepatic steatosis, inflammation, and fibrosis, leading to cirrhosis. These findings provide further evidence of the hepatotoxicity of CA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Shane Kelly, Katherine J. L. Jackson, Timothy J. Peters, Dan Suan, Christopher C. Goodnow
Summary: This study successfully identified and characterized PR3-specific B cells from the peripheral blood of patients with PR3 autoantibodies. These cells exhibited specific immunological features, suggesting that PR3 self-reactivity may occur early in B-cell development.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Ana Merino-Vico, Jan Piet van Hamburg, Paul Tuijnenburg, Giulia Frazzei, Aram Al-Soudi, Carlo G. Bonasia, Boy Helder, Abraham Rutgers, Wayel H. Abdulahad, Coen A. Stegeman, Jan-Stephan Sanders, Laura Bergamaschi, Paul A. Lyons, Theo Bijma, Laura van Keep, Kirsten Wesenhagen, Aldo Jongejan, Henric Olsson, Niek de Vries, Taco W. Kuijpers, Peter Heeringa, Sander W. Tas
Summary: B lineage cells play a critical role in ANCA-associated vasculitis (AAV), and the transcription factor NF-kappa B may be a potential therapeutic target for AAV and other autoimmune diseases with prominent B cell involvement.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Christopher Nelke, Thomas Muentefering, Derya Cengiz, Lukas Theissen, Vera Dobelmann, Christina B. Schroeter, Helena Block, Corinna Preu, Alexander P. E. Michels, Stefanie Lichtenberg, Marc Pawlitzki, Steffen Pfeuffer, Niklas Huntemann, Alexander Zarbock, Thorben Briese, Christoph Kittl, Carsten Dittmayer, Thomas Budde, Ingrid E. Lundberg, Werner Stenzel, Sven G. Meuth, Tobias Ruck
Summary: K2P2.1 plays a regulatory role in the autoimmune response of idiopathic inflammatory myopathies (IIMs), by regulating inflammatory cell response, adhesion, and transmigration in both endothelial and skeletal muscle cells. Inhibiting K2P2.1 enhances the inflammatory response, while activating K2P2.1 improves the disease course.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Xuan Zhang, Jun Xia, Ying Jiang, David S. Pisetsky, Josef S. Smolen, Rong Mu, Shengming Dai, Michael E. Weinblatt, Tore K. Kvien, Juan Li, Thomas Doerner, Yu Zhang, Liwei Lu, Chengde Yang, Pingting Yang, Yuan Zhang, Chenchen Xu, Zhan Zhao, Peter E. Lipsky
Summary: The study suggests that TwHF may be as effective as MTX in treating active RA, and combination therapy may be more effective than monotherapy.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Maya F. Amjadi, Maxwell H. Parker, Ryan R. Adyniec, Zihao Zheng, Alex M. Robbins, S. Janna Bashar, Michael F. Denny, Sara S. Mccoy, Irene M. Ong, Miriam A. Shelef
Summary: Rheumatoid factors (RFs) are polyreactive antibodies that can bind disease-specific epitopes. Recent studies have found that RFs in COVID-19 can bind novel IgG epitopes, which provides new insights into the mechanism of RFs.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Johanne Liberatore, Yann Nguyen, Jerome Hadjadj, Pascal Cohen, Luc Mouthon, Xavier Puechal, Loic Guillevin, Benjamin Terrier
Summary: B-cell depletion induced by rituximab (RTX) in ANCA-associated vasculitis (AAV) can lead to decreased gammaglobulin levels, which is associated with an increased risk of relapse and severe infections. Older age, low gammaglobulin levels, and receiving pulses of methylprednisolone at induction therapy are risk factors for gammaglobulin decline.
JOURNAL OF AUTOIMMUNITY
(2024)
