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Foxp3-expressing CD4 regulatory T (Treg) cells play a crucial role in suppressing autoimmunity, tolerating food antigens and commensal microbiota, and maintaining tissue integrity. These multifaceted functions are guided by environmental cues through interconnected signaling pathways. Traditionally, Treg fate and function were believed to be statically determined by the forkhead box protein Foxp3 that directly binds to DNA. However, this model has not been rigorously tested in physiological and pathological conditions where Treg cells adapt their function in response to environmental cues, raising questions about the contribution of Foxp3-dependent gene regulation to their versatility. Recent research indicates that Foxp3 primarily functions as a transcriptional cofactor, whose chromatin interaction is influenced by other DNA-binding proteins that respond to cell activation, stimulation, or differentiation. This new perspective offers an opportunity to reevaluate Foxp3's activity modes in diverse biological contexts. By exploring this paradigm, we aim to unravel the fundamental principles of Treg cell biology.
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http://dx.doi.org/10.3389/fimmu.2024.1533823 | DOI Listing |
Am J Reprod Immunol
September 2025
Department of Obstetrics and Gynecology, Second XiangYa Hospital of Central South University, Changsha, Hunan, China.
Problem: Preeclampsia (PE) is a leading cause of perinatal maternal and fetal mortality. Clinical and pathological studies suggest that placental and decidual cell dysfunction may contribute to this condition. However, the pathogenesis of PE remains poorly understood.
View Article and Find Full Text PDFJ Exp Med
November 2025
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Host-pathogen interactions involve two critical strategies: resistance, whereby hosts clear invading microbes, and tolerance, whereby hosts carry high pathogen burden asymptomatically. Here, we investigate mechanisms by which Salmonella-superspreader (SSP) hosts maintain an asymptomatic state during chronic infection. We found that regulatory T cells (Tregs) are essential for this disease-tolerant state, limiting intestinal immunopathology and enabling SSP hosts to thrive, while facilitating Salmonella transmission.
View Article and Find Full Text PDFBiotechnol J
September 2025
Department of Biochemical Engineering, University College London, London, UK.
Chimeric antigen receptor T-cell (CAR-T) therapies have demonstrated clinical efficacy in treating haematological malignancies, resulting in multiple regulatory approvals. However, there is a need for robust manufacturing platforms and the use of GMP-aligned reagents to meet the clinical and commercial demands. This study investigates the impact of serum/xeno-free medium (SXFM) and cytokine supplementation on CAR-T cell production in static and agitated culture systems, using 24-well plate G-Rex vessels and 500 mL stirred tank bioreactors (STRs), respectively.
View Article and Find Full Text PDFJCI Insight
September 2025
Arthur D. Riggs Diabetes and Metabolism Research Institute, The Beckman Research Institute, and.
Steroid-refractory gut acute graft-versus-host disease (SR-Gut-aGVHD) is the major cause of nonrelapse death after allogeneic hematopoietic cell transplantation. High numbers of donor-type IL-22+ T cells, IL-22-dependent dysbiosis, and loss of antiinflammatory CX3CR1hi mononuclear phagocytes (MNPs) play critical roles in SR-Gut-aGVHD pathogenesis. CEACAM1 on intestinal epithelial cells (IECs) is proposed to regulate bacterial translocation and subsequent immune responses in the intestine.
View Article and Find Full Text PDFClin Exp Immunol
September 2025
Mucosal Immunology Lab, Department of Paediatrics and Immunology. Universidad de Valladolid. Valladolid. Spain.
Introduction: Although Coeliac disease (CD) current and only treatment is a life-long strict gluten free diet (GFD), some patients suffer from persistent duodenal lesions despite years into the diet. Hence, we aimed to study the effect that the GFD elicits on the mucosal immune infiltrate from these patients.
Method: To that end, duodenal biopsies were collected from non-coeliac controls and CD patients, both at diagnosis and after at least one year into the GFD.