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Current cytokine-based natural killer (NK) cell priming techniques have exhibited limitations such as the deactivation of biological signaling molecules and subsequent insufficient maturation of the cell population during mass cultivation processes. In this study, we developed an amphiphilic trigonal 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-polyethylene glycol (PEG) material to assemble NK cell clusters via multiple hydrophobic lipid insertions into cellular membranes. Our lipid conjugate-mediated ex vivo NK cell priming sufficiently augmented the structural modulation of clusters, facilitated diffusional signal exchanges, and finally activated NK cell population with the clusters. Without any inhibition in diffusional signal exchanges and intrinsic proliferative efficacy of NK cells, effectively prime NK cell clusters produced increased interferon-gamma, especially in the early culture periods. In conclusion, the present study demonstrates that our novel lipid conjugates could serve as a promising alternative for future NK cell mass production.
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http://dx.doi.org/10.3390/ijms25031556 | DOI Listing |
Cell Res
September 2025
Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
The pre-dimerization of endosome-localized RNA sensor Toll-like receptor 3 (TLR3) is required for its innate recognition, yet how TLR3 pre-dimers are formed and precisely primed for innate activation remains unclear. Here, we demonstrate that endosome-localized self RNA Rmrp directly binds to TLR3 and induces TLR3 dimerization in the early endosome but does not interact with endosome-localized TLR7, TLR8, TLR9 or cytoplasmic RNA sensor RIG-I under homeostatic conditions. Cryo-EM structure of Rmrp-TLR3 complex reveals a novel lapped conformation of TLR3 dimer engaged by Rmrp, which is distinct from the activation mechanism by dsRNA and the specific structural feature at the 3'-end of Rmrp is critical for its functional interaction with TLR3.
View Article and Find Full Text PDFRes Vet Sci
September 2025
Laboratorio de Genética Bioquímica LAGENBIO - Instituto de Investigación Sanitaria de Aragón (IIS) - Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, Zaragoza, Spain. El
The allogeneic administration of equine mesenchymal stem/stromal cells (MSCs) has numerous advantages over autologous therapy, but their interactions with the patient's immune system need to be further elucidated. These interactions can be influenced by factors such as the compatibility between donor-receptor for the major histocompatibility complex (MHC) and by the MHC expression levels, which can change under different conditions like inflammatory exposure and chondrogeneic differentiation. In this study, we evaluated the local immune response induced by chondrogeneically differentiated (MSC-chondro), pro-inflammatory primed (MSC-primed) and basal (MSC-naïve) MSCs, and how this response changes the immunomodulatory and immunogenic profiles of MSCs in vivo.
View Article and Find Full Text PDFArch Med Res
September 2025
Universidad Autónoma de Nuevo León, College of Medicine, Biochemistry and Molecular Medicine Department, Monterrey, Mexico; Universidad Autónoma de Nuevo León, Center for Research and Development in Health Sciences, Neurometabolism Unit, Monterrey, Mexico. Electronic address:
Background: Long-chain ceramides have been implicated in anxiety-like behavior and in priming microglial activation, suggesting a possible lipid-immune crosstalk in emotional regulation.
Methods: We systemically administered a mixture of C16:0, C18:0, C22:0, C24:0, and C24:1 ceramides to adult male and female mice. Anxiety-like behavior was assessed with behavioral tests.
ESMO Open
September 2025
Aminex Therapeutics, Inc., Kenmore, USA. Electronic address:
Background: Dysregulation of polyamine synthesis has been observed in various cancer cell types. A novel approach to depriving cancer cells of polyamines involves the use of difluoromethylornithine (DFMO) to block polyamine biosynthesis in combination with AMXT 1501, a potent inhibitor of polyamine transport. Preclinical mouse tumor models showed that the combination of AMXT 1501 plus DFMO had strong antitumor activity, together with evidence of a stimulated immune response against tumors.
View Article and Find Full Text PDFDermatol Ther (Heidelb)
September 2025
Department of Dermatology, Kyoto University, Kyoto, Japan.
Atopic dermatitis (AD) is a chronic inflammatory disease characterized by eczematous skin lesions, intense pruritus, skin pain, sleep disruption, and mental health disturbances. There remains a need for a therapeutic option that delivers durable efficacy, safety, and convenient dosing across the AD patient population. This review provides an overview of AD pathogenesis driven by T-cell imbalance and describes a novel therapeutic option targeting the OX40 receptor, a costimulatory molecule expressed specifically on activated T cells.
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