Review
Biochemistry & Molecular Biology
Heather D. Ots, Jovanna A. Tracz, Katherine E. Vinokuroff, Alberto E. Musto
Summary: CD40-CD40L plays a key role in the central nervous system by upregulating proinflammatory molecules. Its function is well understood in the context of infection, but its role in neurological diseases of non-infectious etiology is unclear. This review examines the role of CD40-CD40L in various neurological diseases and highlights therapeutic advancements targeting the CD40 system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Fabrice Cognasse, Anne Claire Duchez, Estelle Audoux, Theo Ebermeyer, Charles Antoine Arthaud, Amelie Prier, Marie Ange Eyraud, Patrick Mismetti, Olivier Garraud, Laurent Bertoletti, Hind Hamzeh-Cognasse
Summary: Platelets are anucleate cytoplasmic fragments derived from medullary megakaryocytes. They form platelet plugs by adhering to damaged endothelium and secrete growth factors that contribute to platelet aggregation and vascular repair. Platelets also play a major role in inflammation and immune defense through receptors and lectins. Additionally, platelet activation leads to the release of inflammatory mediators and direct activation of immune cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Myrthe E. Reiche, Kikkie Poels, Laura A. Bosmans, Winnie G. Vos, Claudia M. van Tiel, Marion J. J. Gijbels, Suzanne A. B. M. Aarts, Myrthe den Toom, Linda Beckers, Christian Weber, Dorothee Atzler, Patrick C. N. Rensen, Sander Kooijman, Esther Lutgens
Summary: The CD40-CD40L dyad has an important role in chronic inflammatory diseases associated with aging. This study found that CD40 is also present on adipocytes. Deficiency of adipocyte CD40 leads to a decrease in bone marrow hematopoietic stem cells, increased T-cell activation, and elevated corticosterone levels, particularly with age. However, adipocyte CD40 deficiency also reduces atherosclerosis burden and ameliorates diet-induced obesity.
Article
Cardiac & Cardiovascular Systems
Ming Yuan, Bin Wu, Liang Zhang, Huan Wang, Yongjun Yang
Summary: This study investigated the role of CD40L/CD40 in regulating adipokine and cytokine expression in epicardial adipose tissue, showing that CD40 levels were significantly increased in CAD patients. CD40 was found to modulate adipokine and cytokine expression by affecting MLL1, leading to changes in transcription and secretion of related genes.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Laura A. Bosmans, Lena Bosch, Pascal J. H. Kusters, Esther Lutgens, Tom T. P. Seijkens
Summary: Chronic inflammation drives the development of atherosclerosis, for which additional anti-inflammatory therapeutic strategies are required despite optimal treatment of classical cardiovascular risk factors. The CD40-CD40L dyad plays a central role in regulating the inflammatory response during atherosclerosis development, and novel CD40-CD40L targeting strategies show therapeutic potential in cardiovascular medicine.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2021)
Review
Immunology
Alecia M. Blaszczak, Anahita Jalilvand, Willa A. Hsueh
Summary: Adipose tissue inflammation plays a crucial role in obesity and its complications, with adipocytes acting as both endocrine and immunologic cells. The innate immune cells in adipose tissue, such as adipocytes and macrophages, are key players in promoting inflammation. T cells and B cells also contribute to adipose tissue inflammation, highlighting the importance of adaptive immunity in this process.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Michael Lacy, Christina Buerger, Annelie Shami, Maiwand Ahmadsei, Holger Winkels, Katrin Nitz, Claudia M. van Tiel, Tom T. P. Seijkens, Pascal J. H. Kusters, Ela Karshovka, Koen H. M. Prange, Yuting Wu, Sanne L. N. Brouns, Sigrid Unterlugauer, Marijke J. E. Kuijpers, Myrthe E. Reiche, Sabine Steffens, Andreas Edsfeldt, Remco T. A. Megens, Johan W. M. Heemskerk, Isabel Goncalves, Christian Weber, Norbert Gerdes, Dorothee Atzler, Esther Lutgens
Summary: The CD40L-CD40 signaling axis plays a role in atherosclerosis. This study investigates the cell-specific functions of the most relevant CD40L-expressing cell types. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization, while platelet-derived CD40L ameliorates atherothrombosis.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
TingTing Tang, Xiang Cheng, Billy Truong, LiZhe Sun, XiaoFeng Yang, Hong Wang
Summary: The CD40 receptor and its ligand CD40L play a critical role in immune activation, with various therapeutic agents targeting this interaction showing promising clinical efficacy in treating malignancies and autoimmune diseases. The signaling pathways activated by CD40/CD40L interaction lead to immune cell activation and modulation, making it an attractive target for immunotherapy. Ongoing and completed clinical trials have demonstrated the potential of CD40/CD40L-targeted therapy in activating immune responses and treating diseases.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Chemistry, Medicinal
Doha Anka Idrissi, Nezha Senhaji, Asmae Aouiss, Loubna Khalki, Youssef Tijani, Nabil Zaid, Fatima Zahra Marhoume, Abdallah Naya, Mounia Oudghiri, Mostafa Kabine, Younes Zaid
Summary: UC and CD are chronic and multifactorial diseases affecting the intestinal tract, characterized by recurrent inflammation leading to symptoms such as abdominal pain, diarrhea, vomiting, and rectal bleeding. IBD involves defects in the intestinal mucosal barrier in genetically predisposed individuals due to an uncontrolled inflammatory response to normal flora, potentially triggered by environmental factors or specific lifestyle choices. The involvement of the CD40/CD40L platelet complex and IL-1 in the development of IBD, particularly CD, has been extensively studied and may provide insights for future therapeutic approaches targeting these pathways.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Cell & Tissue Engineering
Joelle Dulong, Severine Loisel, Delphine Rossille, Simon Leonard, Nadege Bescher, Isabelle Bezier, Maelle Latour, Celine Monvoisin, Delphine Monnier, Nicolas Bertheuil, David Roulois, Karin Tarte
Summary: This study identified the upregulation of CD40L in adipose tissue and the overexpression of CD40 in ASCs in obese patients. The CD40-CD40L axis plays a crucial role in modulating the interaction between ASCs and neutrophils, highlighting its therapeutic potential.
Article
Medicine, General & Internal
Ewa Migacz, Wioletta Olejarz, Alicja Gluszko, Katarzyna Bednarek-Rajewska, Robert Proczka, David F. Smith, Stacey L. Ishman, Wojciech Kukwa
Summary: This study found that the expression levels of inflammatory markers such as CD40, CD40L, MCP-1, and MMP-9 increased proportionally with the severity of obstructive sleep apnea. However, significant differences among groups were observed only for MCP-1. The increased expression of these inflammatory markers is associated with the severity of OSA, suggesting a potential role of the CD40-CD4-L inflammatory pathway in plaque instability and rupture in OSA patients.
Article
Dermatology
Shilpi Giri, Heikrujam Thoihen Meitei, Amrita Mishra, Girdhari Lal
Summary: This study investigates the mechanistic role of gamma delta T cells in costimulatory blockade-induced transplantation tolerance. Depletion of gamma delta T cells leads to acute rejection of skin allografts despite tolerogen treatment. Tolerogen treatment promotes the generation of regulatory V gamma 2(+) gamma delta T cells and suppresses IFN-gamma production. Adoptive transfer of these regulatory V gamma 2(+) gamma delta T cells prolongs the survival of allografts.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Esther Pototskiy, Katherine Vinokuroff, Andrew Ojeda, C. Kendall Major, Deepak Sharma, Taylor Anderson, Kendall Howard, Alberto E. Musto
Summary: Unregulated neuro-inflammation mediated by CD40-CD40L activation plays a crucial role in seizures in temporal lobe epilepsy. Inhibiting the interaction between CD40 and CD40L can potentially serve as a target for immunotherapy, reducing seizure susceptibility and severity in patients.
SCIENTIFIC REPORTS
(2021)
Article
Food Science & Technology
Liliya V. Vasileva, Martina S. Savova, Daniel Tews, Martin Wabitsch, Milen Georgiev
Summary: Chronic low-grade inflammation is a characteristic of obesity and its metabolic disorders. Signaling from pro-inflammatory factors like TGF-beta or IL-17A is crucial for fibroblast progenitor cells to differentiate into adipocytes. Modulation of inflammation during adipogenic differentiation could be a potential approach to prevent metabolic disorders. Rosmarinic acid (RA), known for its anti-inflammatory effects, has the potential to prevent inflammation and excessive lipid accumulation in human adipocytes, suggesting a potential treatment for obesity and obesity-related inflammation.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Nutrition & Dietetics
Rawan Nehme, Arthur Chervet, Caroline Decombat, Lucie Longechamp, Adrien Rossary, Rebecca Boutin, Amandine Rousset, Francois Senejoux, Caroline Vachias, Celine Auxenfans, Didier Fraisse, Jean-Baptiste Guyon, Edith Filaire, Jean-Yves Berthon, Mona Diab-Assaf, Laetitia Delort, Florence Caldefie-Chezet
Summary: Polyphenols and flavonoids in Rooibos tea can reduce obesity and inflammation by reducing ROS production and pro-inflammatory cytokine secretion, inhibiting macrophage polarization, and decreasing lipid accumulation and adipogenesis.
