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Cell therapy with human IL-10-producing ILC2s limits xenogeneic graft-versus-host disease by inhibiting pathogenic T cell responses.
Cell Rep
December 2024
Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Hospital Research Institute, Ajmera Transplant Centre, University Health Network, Toronto, ON M5G 1L7, Canada. Electronic address:
Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 conferred superior protection from GVHD than IL-10 ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 protective effects, indicating that these cytokines are important for the protective effects of ILC2.
View Article and Find Full Text PDFThe IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.
JCI Insight
December 2024
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Deficits in IL-2 signaling can precipitate autoimmunity by altering the function and survival of FoxP3+ regulatory T cells (Tregs) while high concentrations of IL-2 fuel inflammatory responses. Recently, we showed that the non-beta IL-2 SYNTHORIN molecule SAR444336 (SAR'336) can bypass the induction of autoimmune and inflammatory responses by increasing its reliance on IL-2 receptor α chain subunit (CD25) to provide a bona fide IL-2 signal selectively to Tregs, making it an attractive approach for the control of autoimmunity. In this report, we further demonstrate that SAR'336 can support non-beta IL-2 signaling in murine Tregs and limit NK and CD8+ T cells' proliferation and function.
View Article and Find Full Text PDFMultiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study.
Nat Commun
November 2024
Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg.
Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses.
View Article and Find Full Text PDFThe Major Role of T Regulatory Cells in the Efficiency of Vaccination in General and Immunocompromised Populations: A Review.
Vaccines (Basel)
August 2024
Department of Urology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Article Synopsis
- Vaccines have played a crucial role in controlling pandemics since the smallpox vaccine, including the recent COVID-19 outbreak, by activating various immune cells like CD4 and CD8 T cells and B cells.
- Research shows that specific T regulatory cells, like Treg and Tr1, influence how effective vaccines are, especially for immunocompromised individuals.
- Strategies to enhance vaccine efficacy include adjusting dosages, changing administration routes, giving booster shots, and using monoclonal antibodies to minimize Treg activity and stimulate stronger immune responses.
Effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation: Evidences from diabetic patients and multiple low dose streptozotocin-treated diabetic mice.
J Biochem Mol Toxicol
September 2024
Department of Genetics, Center for Research on Harmful Effects of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Considering detrimental impacts of combustible cigarettes (CCs) on the exacerbation of diabetes mellitus (DM), a significant number of DM patients have substituted CCs with electronic nicotine delivery systems (ENDS). Herewith, we compared CCs and ENDS-dependent modulation of immune cell-driven inflammation in DM patients who used ENDS (DM), CCs (DM) or were non-smokers (DM), paving the way for the better understanding of ENDS-induced biological effects. Multiple low dose streptozotocin (MLD-STZ)-induced mice model of DM was used to support clinical findings.
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