Article
Immunology
Maria Serena Longhi, Giorgina Mieli-Vergani, Diego Vergani
Summary: Regulatory T-cells are crucial for maintaining immune balance and defects can lead to autoimmune attacks; Tregs acquiring effector cell features support the perpetuation of autoimmune damage. In autoimmune liver diseases, Treg impairment is permissive for disease initiation and progression.
JOURNAL OF AUTOIMMUNITY
(2021)
Review
Immunology
Qi Jiang, Guocan Yang, Qi Liu, Shengjun Wang, Dawei Cui
Summary: Rheumatoid arthritis is a systemic and heterogeneous autoimmune disease characterized by symmetrical polyarthritis, with dysfunction of regulatory T (Treg) cells potentially contributing to the breakdown of self-tolerance. The ideal treatment strategy for RA should focus on re-inducing self-tolerance to prevent obvious tissue injury.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Laura Elisa Buitrago-Molina, Julia Pietrek, Fatih Noyan, Jerome Schlue, Michael P. Manns, Heiner Wedemeyer, Matthias Hardtke-Wolenski, Elmar Jaeckel
Summary: Autoimmune hepatitis is a chronic inflammatory disease that requires lifelong immunosuppression, with relapses common after therapy discontinuation. Steroid therapy depletes intrahepatic Tregs, but increasing and strengthening these cells may help in immune regulation restoration. Studies have shown that using complexed IL-2/anti-IL-2 can enhance the Treg compartment and restore balance between Tregs and Teffs, offering new hope for AIH patients.
JOURNAL OF AUTOIMMUNITY
(2021)
Review
Immunology
David W. Scott
Summary: The use of CAR transduced T cells and engineered Tregs with specific receptors show great promise in cancer immunotherapy. Methods involving retroviral transduction of specific T-cell receptors, scFv, or antigens for various diseases models are discussed for their potential clinical translation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Stefan Rosenberger, Reinmar Undeutsch, Reza Akbarzadeh, Justus Ohmes, Philipp Enghard, Gabriela Riemekasten, Jens Y. Humrich
Summary: Treg cells play a regulatory role in controlling the activation and expansion of autoreactive CD4(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Ruoyu Li, Hui Li, Xiaoyan Yang, Huiru Hu, Peidong Liu, Hongbo Liu
Summary: This review summarizes the interaction and protective mechanisms between dendritic cells (DCs) and regulatory T cells (Tregs) in multiple sclerosis (MS), explores their potential value in the treatment of MS, and proposes new therapeutic directions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Qifeng He, Yijun Lu, Wenfang Tian, Runqiu Jiang, Weiwei Yu, Yong Liu, Meiling Sun, Fei Wang, Haitian Zhang, Ning Wu, Zhongjun Dong, Beicheng Sun
Summary: Loss of TOX in thymocytes impairs mTEC maturation and promotes Tγδ17 cell generation, leading to the development of fatal autoimmune hepatitis (AIH). TOX interacts with TCF1 to maintain the balance of γδT cell development, and its expression is negatively correlated with AIH diagnostic score.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Review
Immunology
Aikaterini Hatzioannou, Athina Boumpas, Miranta Papadopoulou, Iosif Papafragkos, Athina Varveri, Themis Alissafi, Panayotis Verginis
Summary: Treg cell plasticity plays a significant role in autoimmunity and cancer, characterized by loss of Foxp3 expression. It has great therapeutic potential through destabilizing Treg cells to promote anti-tumor immunity or enhancing Treg cell stability to attenuate chronic inflammation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Shuyao Qiu, Xiangqian Luo, Lihua Mo, Shuang Zhang, Yun Liao, Li Guan, Liteng Yang, Qinmiao Huang, Dabo Liu, Pingchang Yang
Summary: This study aims to enhance the therapeutic efficacy of allergen-specific immunotherapy (AIT) in experimental allergic rhinitis (AR) by using TAFA4 as an adjuvant. The results show that TAFA4 activates dendritic cells (DCs) in the airway tissues and induces the expression of IL-10, which attenuates the allergic response in mice.
Article
Immunology
Javier Sanchez-Solares, Luis Sanchez, Carmela Pablo-Torres, Celso Diaz-Fernandez, Poul Sorensen, Domingo Barber, Cristina Gomez-Casado
Summary: The study found that CD patients have significantly decreased expression of epithelial junction proteins in their oral mucosa, suggesting compromised barrier integrity. The increase in FoxP3+ cells in CD patients indicates recruitment of Tregs to the damaged mucosa. Amphiregulin mRNA levels in PBMCs and epithelial damage in the oral mucosa correlated with Treg infiltration, suggesting a potential repair phenotype.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Min Hu, Natasha M. Rogers, Jennifer Li, Geoff Y. Zhang, Yuan Min Wang, Karli Shaw, Philip J. O'Connell, Stephen Alexander
Summary: Tregs play a crucial role in kidney transplantation by limiting immune activation and potentially reducing the need for immunosuppression. Studies have shown their importance in improving allo-specific Treg function in both animal and human models.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Meng Li, Arata Itoh, Jingchao Xi, Chunsong Yu, Yuehong Wu, William M. Ridgway, Haipeng Liu
Summary: Efforts to restore immune tolerance to self-antigens without global immune suppression in autoimmune disorders have largely failed. However, modifying peptides with lipophilic compounds significantly enhances antigen presentation and induces immune tolerance, showing promise for the treatment of autoimmune diseases.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Chenglong Wang, Stephen R. Daley
Summary: CD4(+) T cell responses to self-antigens are crucial for immunological self-tolerance. Activation of T-conv cells can cause autoimmune diseases, while activation of T-reg cells is essential to prevent autoimmune diseases. This distinction indicates the importance of the thymus in controlling the differentiation of self-reactive CD4(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Joshua M. Gammon, Sean T. Carey, Vikas Saxena, Haleigh B. Eppler, Shannon J. J. Tsai, Christina Paluskievicz, Yanbao Xiong, Lushen Li, Marian Ackun-Farmmer, Lisa H. Tostanoski, Emily A. Gosselin, Alexis A. Yanes, Xiangbin Zeng, Robert S. Oakes, Jonathan S. Bromberg, Christopher M. Jewell
Summary: The authors have successfully promoted the production of antigen-specific regulatory T cells and prevented the occurrence of type 1 diabetes and allogenic islet transplantation by delivering immune signals to lymph nodes. Antigen-specific tolerance is an important goal in experimental immunotherapy for autoimmune diseases and organ transplantation, as it can selectively inhibit harmful immune responses without compromising protective immunity. However, the current challenge lies in the ineffective control over immune signal targeting, which limits the efficacy and causes non-specific suppression.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Le Zhang, Xuehui Long, Yuye Yin, Jun Wang, Huamin Zhu, Jingjing Chen, Yuliang Wang, Yun Chen, Xiaoming Wang
Summary: Regulatory T cells play important roles in maintaining immune homeostasis and immune tolerance during pregnancy. This study revealed the critical role of H3K36me2 methyltransferase Nsd2 in Treg recruitment at the maternal-fetal interface. Loss of Nsd2 disrupted maternal-fetal immune tolerance, leading to severe fetal loss.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Antonella Avena, Sandro Puggelli, Michael Morris, Andreas Cerny, Alfredo Reparaz Andrade, Emmanuela Pareti, Florian Bihl, Daniele Cassatella, Isabelle Moix, Elisabetta Merlo, Anne-Laure Rougemont, Pietro Majno-Hurst, Diego Vergani, Giorgina Mieli-Vergani, Benedetta Terziroli Beretta-Piccoli
Summary: Half of the adults with unexplained cholestasis and/or recurrent gallstones had ABCB4 variants, suggesting that this condition is underdiagnosed and undertreated, with serious consequences for patients and their families.
DIGESTIVE AND LIVER DISEASE
(2021)
Article
Immunology
Benedetta Terziroli Beretta-Piccoli, Guido Stirnimann, Joachim Mertens, David Semela, Yoh Zen, Luca Mazzucchelli, Anja Voreck, Norbert Kolbus, Elisabetta Merlo, Claudia Di Bartolomeo, Paola Messina, Andreas Cerny, Silvia Costantini, Diego Vergani, Giorgina Mieli-Vergani
Summary: The study found a high proportion of patients with PBC among those with normal ALP levels and positive AMA. Histological diagnosis of PBC was shown in AMA-negative/PBC-specific ANA-positive individuals for the first time, and GGT was identified as a potential biomarker in PBC patients with normal baseline ALP levels. The current guidelines for diagnosing PBC may not cover the full extent of PBC presentation, highlighting the clinical implications for timely treatment initiation.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Gastroenterology & Hepatology
Yun Ma, Haibin Su, Muhammed Yuksel, Maria Serena Longhi, Mark J. McPhail, Pengyun Wang, Sanjay Bansal, Guan-Wee Wong, Jonathon Graham, Li Yang, Richard J. Thompson, Derek G. Doherty, Nedim Hadzic, Yoh Zen, Alberto Quaglia, Michael A. Heneghan, Marianne Samyn, Diego Vergani, Giorgina Mieli-Vergani
Summary: Unique HLA profiles are observed in each subgroup of juvenile autoimmune liver disease, which may be helpful in predicting responsiveness to treatment and disease course.
Article
Immunology
Maria Serena Longhi, Giorgina Mieli-Vergani, Diego Vergani
Summary: Regulatory T-cells are crucial for maintaining immune balance and defects can lead to autoimmune attacks; Tregs acquiring effector cell features support the perpetuation of autoimmune damage. In autoimmune liver diseases, Treg impairment is permissive for disease initiation and progression.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Gastroenterology & Hepatology
Giorgina Mieli-Vergani, Sanjay Bansal, James F. Daniel, Aydan Kansu, Deirdre Kelly, Carmen Martin, Sarah Tizzard, Stefan Wirth, Julian Zhou, Diego Vergani
Summary: In children and adolescents with immune-tolerant CHB, antiviral therapy was found to be ineffective in achieving hepatitis B surface antigen loss, as evaluated in this trial.
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2021)
Article
Allergy
Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani, Diego Vergani
Summary: Circulating autoantibodies are crucial for the diagnosis and classification of autoimmune hepatitis (AIH). The reference method for autoantibody testing remains indirect immunofluorescence, despite limitations. Further studies are needed to validate automated assays as reliable alternatives.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2022)
Review
Gastroenterology & Hepatology
Diego Vergani, Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani
Summary: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized by autoimmune attack on the liver tissue. Standard treatment with steroids and azathioprine is effective for most patients, but alternative treatments may be necessary for non-responsive or intolerant cases. Ongoing research is exploring new therapeutic options targeting B lymphocytes and proinflammatory cytokines to improve treatment outcomes for AIH.
DIGESTIVE AND LIVER DISEASE
(2021)
Review
Gastroenterology & Hepatology
Angelo Di Giorgio, Diego Vergani, Giorgina Mieli-Vergani
Summary: Sclerosing cholangitis is a rare chronic disorder characterized by inflammation and progressive fibrosis of the bile ducts. The most common form in children is associated with autoimmune features and inflammatory bowel disease. The disease can progress to biliary cirrhosis and end-stage liver disease, potentially requiring liver transplantation.
DIGESTIVE AND LIVER DISEASE
(2022)
Article
Immunology
Michele Ghielmetti, Helen Dorothea Schaufelberger, Giorgina Mieli-Vergani, Andreas Cerny, Eric Dayer, Diego Vergani, Benedetta Terziroli Beretta-Piccoli
Summary: This case report describes a 63-year-old man who developed acute severe autoimmune-like hepatitis seven days after receiving the mRNA1273 SARS-CoV-2 vaccine, despite having no history of autoimmunity or natural infection with the virus. The patient displayed unique autoimmune liver serology patterns, including an atypical anti-mitochondrial antibody (AMA) and a distinct type of anti-nuclear antibody (ANA). Treatment with prednisone was effective for this emerging condition.
JOURNAL OF AUTOIMMUNITY
(2021)
Letter
Pediatrics
Marianne Samyn, Kai Hensel, Nedim Hadzic, Giorgina Mieli-Vergani
JOURNAL OF PEDIATRICS
(2022)
Article
Pediatrics
Kai O. Hensel, Eirini Kyrana, Nedim Hadzic, Jake Mann, Giorgina Mieli-Vergani, Marco Gasparetto, Robert Heuschkel, Gabriele Noble-Jamieson, Marianne Samyn
Summary: This study describes the characteristics and clinical course of children and young persons with IBD and SC, finding that prompt diagnosis of SC can improve clinical outcomes.
JOURNAL OF PEDIATRICS
(2021)
Review
Immunology
Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani, Diego Vergani
Summary: Autoimmune hepatitis is an inflammatory liver disease affecting all ages, with type 1 and type 2 having different autoantibodies and predisposing factors, typically responding well to treatment with steroids and azathioprine.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Jonathon J. Graham, Sujit Mukherjee, Muhammad Yuksel, Rebeca Sanabria Mateos, Tengfei Si, Zhenlin Huang, Xiahong Huang, Hadil Abu Arqoub, Vishal Patel, Mark McPhail, Yoh Zen, Nigel Heaton, Maria Serena Longhi, Michael A. Heneghan, Rodrigo Liberal, Diego Vergani, Giorgina Mieli-Vergani, Yun Ma, Bu'Hussain Hayee
Summary: The study found that the gut homing hypothesis is not the primary driver of PSC, and aberrant recruitment of gut-derived T cells to the liver is also seen in other chronic liver diseases. This finding provides a new understanding of the pathogenesis of PSC and CLD.
Review
Gastroenterology & Hepatology
Simon Pape, Romee J. A. L. M. Snijders, Tom J. G. Gevers, Oliver Chazouilleres, George N. Dalekos, Gideon M. Hirschfield, Marco Lenzi, Michael Trauner, Michael R. Manns, John M. Vierling, Aldo J. Montano-Loza, Ansgar W. Lohse, Christoph Schramm, Joost P. H. Drenth, Michael A. Heneghan
Summary: The International Autoimmune Hepatitis Group proposed a consensus on response criteria and endpoints in autoimmune hepatitis, defining terms like complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment to guide future reporting.
JOURNAL OF HEPATOLOGY
(2022)
Editorial Material
Gastroenterology & Hepatology
Giorgina Mieli-Vergani, Yoh Zen, Diego Vergani
LIVER INTERNATIONAL
(2022)