Review
Immunology
Matthew Clark, Charles J. Kroger, Qi Ke, Roland M. Tisch
Summary: TCR signaling plays a crucial role in the development of T cells and the formation of self-reactive T cells, particularly in type 1 diabetes.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Maki Nakayama, Aaron W. Michels
Summary: TCRs serve as unique markers that define antigen specificity for T cells, making them prime candidates for next-generation T cell biomarkers. Developing TCR biomarkers for T1D could potentially provide powerful tools for assessing disease activity and treatment development in diabetes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Angela M. Mitchell, Aimon A. Alkanani, Kristen A. McDaniel, Laura Pyle, Kathleen Waugh, Andrea K. Steck, Maki Nakayama, Liping Yu, Peter A. Gottlieb, Marian J. Rewers, Aaron W. Michels
Summary: In type 1 diabetes, T-cell responses to hybrid insulin peptides (HIPs) may precede clinical symptoms and be associated with disease progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Leeana D. Peters, Wen- Yeh, Juan M. Arnoletti, Matthew E. Brown, Amanda L. Posgai, Clayton E. Mathews, Todd M. Brusko
Summary: The autoimmune pathogenesis of T1D involves immune cell infiltration into pancreatic islets. CD8(+) T cells play a primary role in killing insulin-producing beta-cells. This study demonstrates the engineering of human T cells to improve the specificity and function of autoreactive CD8(+) T cells, potentially leading to cellular therapeutics for treating autoimmunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Farooq Riaz, Ping Wei, Fan Pan
Summary: This review highlights the multifaceted roles of Peroxisome Proliferator-Activated Receptors (PPARs) in T-cell-mediated autoimmune type 1 diabetes (T1D), shedding light on their potential as regulators of immune responses and beta-cell biology. Recent research has elucidated the intricate interplay between CD4+ T cell subsets, such as Tregs and Th17, in developing autoimmune diseases like T1D. PPARs, initially recognized for their role in lipid metabolism, have emerged as potent modulators of inflammation in T1D.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Endocrinology & Metabolism
Mengdi Zhang, Yanyan Zhou, Zhiguo Xie, Shuoming Luo, Zhiguang Zhou, Jiaqi Huang, Bin Zhao
Summary: This review discusses the metabolic reprogramming of T cells in the development of T1D, as well as the key metabolic pathways and regulators that modulate T cell homeostasis, differentiation, and function. Metabolic intervention can be used to suppress autoreactive T cells and limit the progression of beta-cell destruction.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Qing Ling, Lei Shen, Wei Zhang, DuoDuo Qu, Hongdong Wang, Bin Wang, Yong Liu, Jing Lu, Dalong Zhu, Yan Bi
Summary: The study revealed that plasmablasts may function as antigen-presenting cells and promote the activation and proinflammatory response of CD4(+) T cells, contributing to the T cell-mediated beta cell destruction. This suggests potential translational strategies for inhibiting T1D development.
MOLECULAR MEDICINE
(2022)
Review
Immunology
Stuart Mannering, Alan F. Rubin, Ruike Wang, Pushpak Bhattacharjee
Summary: Hybrid insulin peptides (HIPs) are a novel type of neoepitope formed by fusion of two unrelated peptide fragments, recognized by pathogenic CD4(+) T cells and implicated in the immune pathogenesis of type 1 diabetes. Identifying new HIPs is crucial for monitoring changes in T cell mediated beta-cell autoimmunity and developing antigen-specific therapies for type 1 diabetes. However, the vast number of potential HIPs poses technical challenges in their identification.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Angela M. Mitchell, Aaron W. Michels
Summary: Despite progress in understanding the mechanisms behind autoimmune diseases, there is limited knowledge about protective mechanisms against these diseases. In the case of type 1 diabetes, pathogenic T cells that destroy pancreatic islets are well understood, but the immune-mediated mechanisms that contribute to protection against this disease are not fully elucidated. One potential protective mechanism involves regulatory CD4 T cells that suppress immune responses by recognizing self-peptides from islets. This review summarizes current knowledge about the antigenic self-peptides recognized by Tregs in the context of type 1 diabetes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Multidisciplinary Sciences
Todd M. Brusko, Holger A. Russ, Cherie L. Stabler
Summary: Advancements in blood glucose monitoring and therapeutic insulin administration have improved the quality of life for individuals with type 1 diabetes, but still fall short of the metabolic control provided by native islets. Integrated advancements in islet cell replacement and immunomodulatory therapies are offering hope for the restoration of endogenous glucose regulation. Progress in stem cell biology and graft site design are providing innovative sources for cellular material and improved engraftment.
Article
Endocrinology & Metabolism
Pauline Faucher, Frederic Beuvon, Daniela Fignani, Guido Sebastiani, Georgia Afonso, Zhicheng Zhou, Bertrand Dousset, Christian Boitard, Francesco Dotta, Roberto Mallone, Etienne Larger
Summary: Despite persistent GADA and histopathological insulitis findings with decreased beta cell area 6 years after diabetes diagnosis, this case study shows that good glycemic control was maintained with low-dose insulin for up to 8 years post-surgery. Regulated T cell responses to beta cell antigens and FOXP3-positive peri-insulitis suggest long-term spontaneous regulation of islet autoimmunity after significant beta cell loss, with eventual autoimmune progression upon anti-ZnT8 seroconversion.
Review
Immunology
Susanna Esposito, Elena Mariotti Zani, Lisa Torelli, Sara Scavone, Maddalena Petraroli, Viviana Patianna, Barbara Predieri, Lorenzo Iughetti, Nicola Principi
Summary: Type 1 diabetes is the most common pediatric endocrine disease with an increased infection risk and lower immune response to vaccines; further research is needed to establish the most effective and safe vaccine use in this population.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Roberto Mallone, Clementine Halliez, Jinxiu Rui, Kevan C. Herold
Summary: Recent reports have renewed interest in the active role of beta-cells in the pathogenesis of type 1 diabetes. Some studies suggest that type 1 diabetes may primarily be a disease of beta-cells, with autoimmunity playing a secondary role. This perspective encourages the search for environmental triggers that damage beta-cells, and highlights the potential of beta-cells to amplify autoimmune vulnerability and eventually undergo self-destruction. On the other hand, beta-cells also mount protective mechanisms, which may offer novel therapeutic targets for combining immunomodulatory and beta-cell protective agents.
Review
Endocrinology & Metabolism
Kriti Joshi, Fergus Cameron, Swasti Tiwari, Stuart I. Mannering, Andrew G. Elefanty, Edouard G. Stanley
Summary: Induced pluripotent stem cell (iPSC) technology is increasingly used to create in vitro models of monogenic human disorders, while complex conditions like autoimmune Type 1 diabetes (T1D) may require consideration of polygenic inheritance and environmental factors. Models for T1D should be aware of the importance of cell interactions and genetic backgrounds for more accurate representation of the disease.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Silvia Garavelli, Francesco Prattichizzo, Antonio Ceriello, Mario Galgani, Paola de Candia
Summary: Type 1 diabetes is characterized by autoimmune destruction of insulin-secreting beta cells. Recent research suggests that extracellular vesicles (EVs) may serve as biomarkers and therapeutic targets for disease progression and complications.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Oncology
Sana Belkahla, Abrar Ul Haq Khan, Delphine Gitenay, Catherine Alexia, Claire Gondeau, Dang-Nghiem Vo, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Guillaume Cartron, Javier Hernandez, Martine Daujat-Chavanieu, Nerea Allende-Vega, Martin Villalba Gonzalez
Article
Multidisciplinary Sciences
Abrar Ul Haq Khan, Nerea Allende-Vega, Delphine Gitenay, Johan Garaude, Dang-NghiemVo, Sana Belkhala, Sabine Gerbal-Chaloin, Claire Gondeau, Martine Daujat-Chavanieu, Cecile Delettre, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Alberto Anel, Jose M. Cuezva, Jose A. Enriquez, Guillaume Cartron, Charles-Henri Lecellier, Javier Hernandez, Martin Villalba
SCIENTIFIC REPORTS
(2018)
Article
Medicine, Research & Experimental
Patricia Luz-Crawford, Gabriel Espinosa-Carrasco, Natacha Ipseiz, Rafael Contreras, Gautier Tejedor, Daniel A. Medina, Ana-Maria Vega-Letter, Devi Ngo, Eric F. Morand, Jerome Pene, Javier Hernandez, Christian Jorgensen, Farida Djouad
Article
Immunology
Gabriel Espinosa-Carrasco, Cecile Le Saout, Pierre Fontanaud, Thomas Stratmann, Patrice Mollard, Marie Schaeffer, Javier Hernandez
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Multidisciplinary Sciences
Emmanuelle Coque, Celine Salsac, Gabriel Espinosa-Carrasco, Bela Varga, Nicolas Degauque, Marion Cadoux, Roxane Crabe, Anais Virenque, Claire Soulard, Julie K. Fierle, Alexandre Brodovitch, Margot Libralato, Attila G. Vegh, Stephanie Venteo, Frederique Scamps, Jose Boucraut, David Laplaud, Javier Hernandez, Csilla Gergely, Thierry Vincent, Cedric Raoul
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Cell & Tissue Engineering
Patricia Luz-Crawford, Javier Hernandez, Farida Djouad, Noymar Luque-Campos, Andres Caicedo, Severine Carrere-Kremer, Jean-Marc Brondello, Marie-Luce Vignais, Jerome Pene, Christian Jorgensen
STEM CELL RESEARCH & THERAPY
(2019)
Article
Immunology
Catherine Alexia, Mailys Cren, Pascale Louis-Plence, Dang-Nghiem Vo, Yasamine El Ahmadi, Emilie Dufourcq-Lopez, Zhao-Yang Lu, Javier Hernandez, Farkhad Shamilov, Olga Chernysheva, M. Vasilieva, I. Vorotnikov, Yana Vishnevskay, Nikolay Tupitsyn, Jean-Francois Rossi, Martin Villalba
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Oncology
Chantal Reina-Ortiz, Michael Constantinides, Alexis Fayd-Herbe-de-Maudave, Jessy Presumey, Javier Hernandez, Guillaume Cartron, Rosana Diez, Isabel Izquierdo, Gemma Azaceta, Luis Palomera, Isabel Marzo, Javier Naval, Alberto Anel, Martin Villalba, David Giraldosa
Summary: The study evaluated the potential of expanded NK cells from two sources combined with mAbs to target primary multiple myeloma cells. Results indicate that umbilical cord blood eNKs are highly cytotoxic against MM cells, while peripheral blood eNKs have significant cytotoxic advantage when combined with daratumumab.
Article
Multidisciplinary Sciences
Sana Belkahla, Joaquin Marco Brualla, Alexis Fayd'herbe de Maudave, Paolo Falvo, Nerea Allende-Vega, Michael Constantinides, Abrar Ul Haq Khan, Lois Coenon, Catherine Alexia, Giulia Mitola, Paul Massa, Stefania Orecchioni, Francesco Bertolini, Wissem Mnif, Javier Hernandez, Alberto Anel, Martin Villalba
Summary: Leukemic cells adapt their metabolism to support their fast proliferation and can be recognized by immune cells through activating receptors. The tumor suppressor gene p53 plays a role in cell metabolism and the expression of ligands involved in immune recognition. A chemical compound called dichloroacetate (DCA) induces the expression of these ligands in tumor cells with functional p53, sensitizing them to cytotoxic lymphocytes. DCA treatment also slows down tumor growth in vivo and could potentially enhance the effectiveness of immunotherapies using CAR T cells or NK cells.
SCIENTIFIC REPORTS
(2022)
Article
Endocrinology & Metabolism
Aurelien Michau, Chrystel Lafont, Paula Bargi-Souza, Yasmine Kemkem, Anne Guillou, Magalie A. Ravier, Gyslaine Bertrand, Annie Varrault, Tatiana Fiordelisio, David J. Hodson, Patrice Mollard, Marie Schaeffer
Summary: Pancreatic islet vascular cells, particularly pericytes, play a crucial role in regulating insulin release and maintaining beta cell function. However, metabolic stress, such as obesity, can lead to pericyte hypertrophy and impaired vascular responses, which may contribute to beta cell failure in type 2 diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell & Tissue Engineering
Waseem Akhter, Jean Nakhle, Loic Vaillant, Genevieve Garcin, Cecile Le Saout, Matthieu Simon, Carole Crozet, Farida Djouad, Christian Jorgensen, Marie-Luce Vignais, Javier Hernandez
Summary: Mesenchymal stem/stromal cells (MSCs) have the ability to transfer their own mitochondria to neighboring cells, thereby suppressing CD4(+) Th1 immune responses and exerting immunomodulatory effects. The transferred MSC mitochondria can inhibit the activation, proliferation, and production of interferon gamma in CD4(+) T cells, and also prevent the upregulation of the Th1 transcription factor T-bet. This mitochondrial transfer may represent a general mechanism of MSC-dependent immunosuppression.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Medicine, Research & Experimental
Nicola Romano, Chrystel Lafont, Pauline Campos, Anne Guillou, Tatiana Fiordelisio, David J. Hodson, Patrice Mollard, Marie Schaeffer
Summary: Central integration of peripheral appetite-regulating signals is crucial for maintaining energy homeostasis. This study investigated the role of median eminence mural cells in modulating gut hormone effects on feeding behavior. The findings suggest that activation of these vascular cells can alter blood flow velocity, delaying the access of ghrelin to target neurons and thereby modulating food intake in response to peripheral ghrelin.
Article
Cell Biology
Marie Schaeffer, Marcelo Nollmann
Summary: Eukaryotic genomes are organized in 3D in a multiscale manner, and different mechanisms acting at each of these scales can contribute to transcriptional regulation. However, the large single-cell variability in 3D chromatin structures represents a challenge to understand how transcription may be differentially regulated between cell types in a robust and efficient manner.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2023)
Article
Genetics & Heredity
Ayla Secio-Silva, Felipe Emrich, Paulo H. Evangelista-Silva, Rodrigo Pereira Prates, Andressa Harumi Torelli Hijo, Tatienne Neder Figueira-Costa, Marie Schaeffer, Francemilson Goulart-Silva, Rodrigo Antonio Peliciari-Garcia, Paula Bargi-Souza
Summary: This study investigated the expression and stability of potential housekeeping genes (HKGs) in tissues of HFD-treated mice. The most stable HKGs were determined in different tissues, and some unsuitable HKGs were also identified. These findings provide valuable guidance for RT-qPCR analysis in studies of energy metabolism regulation in HFD mice models.