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)
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
Linda M. Lee, Hong Zhang, Karim Lee, Horace Liang, Alexander Merleev, Flavio Vincenti, Emanual Maverakis, Angus W. Thomson, Qizhi Tang
Summary: In this study comparing arTregs expanded ex vivo using different types of antigen-presenting cells, it was found that sDCs stimulated Tregs to expand in much larger numbers. Additionally, sDC-generated arTregs expressed higher levels of CD80, CD86, and T cell-attracting chemokines, indicating their superior expansion-inducing capacity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ching-Lien Wu, Julien Caumartin, Giada Amodio, Francois Anna, Maria Loustau, Silvia Gregori, Pierre Langlade-Demoyen, Joel LeMaoult
Summary: Invariant Natural Killer T (iNKT) cells, when activated by exogenic glycolipid antigen, can release cytokines rapidly to enhance anti-tumor activity. The presence of the tolerogenic molecule HLA-G in humans may impact the function of iNKT cells, potentially affecting the outcome of clinical trials.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Sara Ness, Shiming Lin, John R. Gordon
Summary: Dendritic cells are antigen-presenting cells that interact with T cells to regulate adaptive immune responses. Under certain conditions, dendritic cells can develop into anti-inflammatory cells, inducing immunologic tolerance. Studies have shown that regulatory dendritic cells induce T cell tolerance by suppressing effector T cells and inducing regulatory T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Daniel S. Shin, Sneha Ratnapriya, Creel Ng Cashin, Lucy F. Kuhn, Rod A. Rahimi, Robert M. Anthony, James J. Moon
Summary: Self-antigen-specific T cells are regulated through tolerance mechanisms, but tissue injury can disrupt this regulation and trigger autoimmunity. Using mouse models of lung injury, we found that acute injury leads to the expansion of CD4+ regulatory T cells (Tregs) that specifically recognize self-antigen. Conventional CD4+ T cells with the same self-antigen specificity remained unresponsive even after Treg ablation. Therefore, the self-antigen-specific CD4+ T cell repertoire plays a regulatory role in limiting tissue damage and autoimmunity during acute injury.
Article
Immunology
Yannick D. Muller, Leonardo M. R. Ferreira, Emilie Ronin, Patrick Ho, Vinh Nguyen, Gaetano Faleo, Yu Zhou, Karim Lee, Kevin L. Leung, Nikolaos Skartsis, Anupurna M. Kaul, Arend Mulder, Frans H. J. Claas, James A. Wells, Jeffrey A. Bluestone, Qizhi Tang
Summary: The study demonstrates that genome-engineered mono-antigen-specific A2-CAR Tregs can localize to HLA-A2-expressing grafts and exhibit antigen-dependent in vivo suppression. These Tregs do not impair the function of islets and can delay graft-versus-host disease. This approach may be applied towards developing precision Treg cell therapies for transplant tolerance.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Ke-jia Wu, Qu-fei Qian, Jin-ren Zhou, Dong-lin Sun, Yun-fei Duan, Xi Zhu, Kurt Sartorius, Yun-jie Lu
Summary: The human liver plays crucial roles in synthesizing extracellular matrix (ECM) and regulating fibrogenesis for maintaining homeostasis. Chronic liver injury induces fibrogenesis due to the imbalance between ECM accumulation and fibrosis resolution. Liver diseases that cause fibrogenesis are associated with various risk factors, including hepatitis infection, schistosomiasis, alcohol, certain drugs, toxicants, diabetes, and obesity. Hepatic stellate cells (HSCs) activation, which generate and accumulate ECM, is a key event in liver fibrosis. The paper reviews the dual role of regulatory T-cells (Tregs) in liver fibrogenesis, including their promotion of immunosuppression and activation of fibrosis. Understanding the contradictory roles of Tregs in different immune microenvironments and molecular pathways is important for managing liver fibrosis.
CELL DEATH DISCOVERY
(2023)
Review
Immunology
Herman Waldmann
Summary: The field of tissue transplantation is moving towards harnessing physiological mechanisms of self-tolerance, with the recent discovery of Treg playing a crucial role. Despite limited knowledge on how Treg function in averting transplant rejection, therapeutic needs are driving the utilization of Treg as agents to potentially replace or complement current drug combinations.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Review
Cell Biology
Xiaodong Du, Mingqian Li, Chen Huan, Guoyue Lv
Summary: This review discusses the origin, maturation, migration, and pathological effects of dendritic cell subsets in liver transplantation, as well as their roles in transplant rejection and tolerance. The latest progress in dendritic cell-based treatment regimens is also outlined.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Immunology
Yi Zhang, Lei Li, Genevieve Genest, Wei Zhao, Dan Ke, Sabrina Bartolucci, Nils Pavey, Tho-Alfakar Al-Aubodah, Duncan Lejtenyi, Bahar Torabi, Moshe Ben-Shoshan, Bruce Mazer, Ciriaco A. Piccirillo
Summary: In this study, the induction of specific T-REG cells during oral immunotherapy (OIT) in children with cow's milk protein (CMP) allergy was found to be effective in promoting tolerance and reducing Th2 responses. The expansion of these T-REG cells correlated with successful desensitization to CMP and may be a potential marker for predicting the time to reach maintenance phase in OIT.
FRONTIERS IN IMMUNOLOGY
(2021)
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
Jer-Hwa Chang, Hsiao-Chi Chuang, George Hsiao, Tsung-Yun Hou, Ching-Chiung Wang, Shih-Chun Huang, Bo-Yi Li, Yueh-Lun Lee
Summary: Acteoside can suppress the production of proinflammatory mediators by dendritic cells and enhance the secretion of anti-inflammatory cytokines. It can also promote the generation of regulatory T cells through aryl hydrocarbon receptor activation. In a mouse model of allergic asthma, acteoside can reduce Th2-type cytokine levels, increase the levels of anti-inflammatory cytokines and the frequency of regulatory T cells, and ameliorate asthma symptoms and pulmonary inflammation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Immunology
Jessica G. Lee, Kathleen E. Jaeger, Yoichi Seki, Yi Wei Lim, Christina Cunha, Aleksandra Vuchkovska, Alexander J. Nelson, Anya Nikolai, Dan Kim, Michael Nishimura, Katherine L. Knight, Paula White, Makio Iwashima
Summary: The study reveals that a subset of CD14(+) monocytes can generate regulatory Foxp3(+) T-bet(+) T cells from umbilical cord blood, which suppress T-cell proliferation and ameliorate graft-versus-host disease. Additionally, adult peripheral blood monocytes are capable of inducing Foxp3(+) T cells, but their induction is inhibited by lymphoid cells from adult peripheral blood in neonates. This suggests a novel immunoregulatory role of monocytes in generating regulatory T cells with implications for both neonates and adults.
Article
Immunology
Bin Cui, Xiao-Jie Chen, Jie Sun, Shi-Peng Li, Guang-Peng Zhou, Li-Ying Sun, Lin Wei, Zhi-Jun Zhu
Summary: Exosomal miR-193b-3p derived from DCs promotes the differentiation of Treg cells by inhibiting NLRP3 expression. These findings provide new insights into the immunoregulatory mechanisms after liver transplantation and offer potential for the treatment or prevention of allograft rejection.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Surgery
Tommy Ivanics, Rodrigo Vianna, Chandrashekhar A. Kubal, Kishore R. Iyer, George Mazariegos, Cal S. Matsumoto, Richard Mangus, Thiago Beduschi, Marwan Abouljoud, Jonathan A. Fridell, Shunji Nagai
Summary: The update in liver allocation from DSA to AC had varying impacts on waitlist mortality and transplant probability for patients listed for combined liver-intestine transplantation, with lower transplant probability observed in adults but similar outcomes in pediatric patients. Additionally, there was a decrease in the proportion of patients who underwent transplant with exception points post-AC. Efforts should be made to ensure equitable organ allocation in this vulnerable patient population.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Julia M. Boster, Riccardo Superina, George Mazariegos, Gregory M. Tiao, Jonathan P. Roach, Mark A. Lovell, Brian S. Greffe, George Yanni, Daniel H. Leung, Scott A. Elisofon, Suzanne McDiarmid, Nitika A. Gupta, Steven J. Lobritto, Caroline Lemoine, Janis M. Stoll, Bernadette E. Vitola, James F. Daniel, Blayne A. Sayed, Dev M. Desai, Abigail E. Martin, Arpit Amin, Ravinder Anand, Sarah G. Anderson, Shikha S. Sundaram
Summary: Management of unresectable pediatric hepatoblastoma and hepatocellular carcinoma remains challenging. This study examined survival predictors in pediatric liver transplantation for these tumors using the SPLIT database. The results showed favorable outcomes after liver transplantation for pediatric hepatoblastoma and hepatocellular carcinoma, including salvage transplant. Unexpected numbers of transplants occurred in PRE/POST-TEXT I/II tumors. Judicious patient selection is critical to distinguish potentially resectable tumors and advocate for organ transplantation in patients with unresectable malignancies.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Pediatrics
Paola Andrea Vargas, Jonathan Michael Cullen, Christina Dalzell, Frank DiPaola, Shawn Pelletier, Kyle A. Soltys, George Vincent Mazariegos, Jose Oberholzer, Nicolas Goldaracena
Summary: This study reviewed 37 split liver transplantations (SLT) conducted at a single center from 2010 to 2019, showing a significant increase in SLT numbers after the introduction of a combined pediatric program and high survival rates in both adult and pediatric recipients.
PEDIATRIC TRANSPLANTATION
(2022)
Article
Pediatrics
Yu-Tang Chang, Kyle Soltys, Ajai Khanna, Geoffrey J. Bond, Armando Ganoza, Jeffrey A. Rudolph, Rakesh Sindhi, George Mazariegos
Summary: This study analyzed the long-term outcomes of transplants using donors younger than 1 year old and found that it was associated with improved graft survival. Optimal utilization of these donors for toddler candidates could increase intestine availability, reduce waiting time, and potentially improve long-term outcomes.
PEDIATRIC TRANSPLANTATION
(2022)
Article
Pediatrics
Vikram K. Raghu, Rita Sico, Jeffrey A. Rudolph, George Mazariegos, Judy Squires, James E. Squires
Summary: This study provides the first report of sarcopenia in pediatric intestinal transplantation, finding a high prevalence without association with worse outcomes. Sarcopenic patients may have improved graft survival, with potential underlying mechanisms for further exploration.
PEDIATRIC TRANSPLANTATION
(2022)
Article
Gastroenterology & Hepatology
James E. Squires, Jacob Bilhartz, Kyle Soltys, Einar Hafberg, George Mazariegos, Nitika A. Gupta, Ravinder Anand, Sarah G. Anderson, Tamir Miloh
Summary: With advances in surgical techniques and medical management, children who receive a liver transplantation can expect remarkable outcomes early after transplant. However, long-term graft loss and mortality rates have not improved. Despite changes in patient selection and no significant improvement in perioperative complications, significant improvements in graft loss and a trend towards improvement in mortality were observed in a more contemporary cohort of children receiving a liver transplantation.
LIVER TRANSPLANTATION
(2022)
Editorial Material
Gastroenterology & Hepatology
George V. Mazariegos, Kyle A. Soltys, Emily R. Perito
LIVER TRANSPLANTATION
(2023)
Editorial Material
Gastroenterology & Hepatology
Kyle Soltys, George Mazariegos, John Bucuvalas
LIVER TRANSPLANTATION
(2022)
Editorial Material
Pediatrics
George V. Mazariegos, Rakesh Sindhi, Armando Ganoza, Kyle Soltys
PEDIATRIC TRANSPLANTATION
(2023)
Review
Pediatrics
Michael Green, James E. Squires, Richard E. Chinnock, Patrizia Comoli, Lara Danziger-Isakov, Daniel E. Dulek, Carlos O. Esquivel, Britta Hocker, Arnaud G. L'Huillier, George Vincent Mazariegos, Gary A. Visner, Catherine M. Bollard, Anne Dipchand, Judith A. Ferry, Thomas G. Gross, Robert Hayashi, Britta Maecker-Kolhoff, Stephen Marks, Olivia M. Martinez, Diana M. Metes, Marian G. Michaels, Jutta Preiksaitis, Francoise Smets, Stephen H. Swerdlow, Ralf U. Trappe, James D. Wilkinson, Upton Allen, Steven A. Webber, Vikas R. Dharnidharka
Summary: This report reviews the existing literature on immunoprophylaxis and chemoprophylaxis for post-transplant lymphoproliferative disorder in children after solid organ transplantation. However, due to insufficient or conflicting evidence, no specific recommendations can be made for the use of any prophylactic or alternative pre-emptive strategy.
PEDIATRIC TRANSPLANTATION
(2022)
Review
Pediatrics
Lisa Remaley, Chethan Ashokkumar, Kyle A. Soltys, George Vincent Mazariegos, Geoffrey James Bond, Ajai Khanna, Armando Ganoza, Miguel Reyes-Mugica, Adriana Zeevi, Rakesh Sindhi
Summary: This study reports a third case of operational tolerance after intestine transplantation, confirming donor-specific hyporesponsiveness in the recipient. The three cases of operational tolerance share common characteristics of a relatively large donor antigenic load transmitted during transplantation and donor-specific hyporesponsiveness. Enhanced donor-induced apoptosis of recipient T-cells may be a mechanistic link between antigenic load and donor-specific hyporesponsiveness.
PEDIATRIC TRANSPLANTATION
(2023)
Article
Surgery
Masaki Yamada, Camila Macedo, Kevin Louis, Tiange Shi, Douglas Landsittel, Christina Nguyen, Masayoshi Shinjoh, Marian G. Michaels, Brian Feingold, George V. Mazariegos, Michael Green, Diana Metes
Summary: Chronic Epstein-Barr virus (EBV) infection is a significant problem after pediatric organ transplantation, especially in heart transplant recipients with high viral load. This study analyzed the immune characteristics of CD8(+)/CD4(+) T cells in pediatric heart, kidney, and liver transplant recipients, and identified distinct phenotypic and transcriptomic profiles in heart HVL carriers. The results suggest different incidences of EBV complications and provide insights for risk stratification and clinical management in different types of transplant recipients.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Gastroenterology & Hepatology
George V. Mazariegos, Emily R. Perito, James E. Squires, Kyle A. Soltys, Adam D. Griesemer, Sarah A. Taylor, Eric Pahl
Summary: This retrospective analysis of OPTN data from 2004 to 2020 evaluated the impact of technical variant grafts (TVGs) on waitlist and transplant outcomes for pediatric liver transplant candidates. The study found that higher utilization of TVGs, particularly from deceased donors or living donors, was significantly associated with lower waitlist mortality. Therefore, increasing the utilization of TVGs is critical to decrease waitlist mortality.
LIVER TRANSPLANTATION
(2023)
Review
Pediatrics
Vikrant Sood, Eliza J. Lee, Vikram Raghu, Miguel Reyes-Mugica, Claudia M. Salgado, James Squires, George Mazariegos
Summary: This study presents a unique case of using A1ATD heterozygote donors for pediatric patients with A1ATD, providing initial evidence that it is safe and effective, thereby expanding the donor pool.
PEDIATRIC TRANSPLANTATION
(2023)
Review
Gastroenterology & Hepatology
Christian Appenzeller-Herzog, Aurelie Rosat, Tim Mathes, Alberto Baroja-Mazo, Andrzej Chruscinski, Sandy Feng, Ignacio Herrero, Maria-Carlota Londono, George Mazariegos, Hidenori Ohe, Jose A. Pons, Alberto Sanchez-Fueyo, Kayo Waki, Julien Vionnet
Summary: Pre-withdrawal time has a significant impact on the success or failure of immunosuppression withdrawal in liver transplant recipients, according to a systematic review and meta-analysis.
LIVER INTERNATIONAL
(2023)