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Updated: Jan 8, 2026
A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes
Published on: April 11, 2025
Monovalent mannose-glycoconjugates of sulforaphane reprogram human dendritic cells via NFATc1 to induce immune
María Elena Angarita-Planchez1, Camila Leiva-Castro1, Ana M Múnera-Rodríguez1,2
1Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain.
Background And Purpose:
Immune tolerance prevents inflammation and autoimmunity, with dendritic cells (DCs) playing a key role. Reprogramming DCs towards a tolerogenic state represents a promising therapeutic strategy. Sulforaphane (SFN) has known immunomodulatory effects, but its clinical application is limited by poor stability and bioavailability. To enhance its therapeutic potential, SFN was conjugated with mannose (SFNMan) or fucose (SFNFuc), aiming to induce a tolerogenic phenotype in human monocyte-derived DCs (moDCs) under inflammation and to explore NFATc1's involvement.
Experimental Approach:
moDCs were exposed to inflammatory conditions and treated with SFN, SFNMan or SFNFuc. Their phenotype, cytokine profile, T cell-modulating capacity and NFATc1 signalling were evaluated.
Key Results:
SFNMan selectively induced a tolerogenic phenotype, characterised by an increased PD-L1/CD86 ratio and IL-10 production; up-regulation of SOCS1 and IDO transcripts; and Treg expansion and reduced proliferation of cytotoxic T cell proliferation. Functional assays and confocal microscopy revealed that SFNMan, but not SFNFuc, promoted NFATc1 nuclear translocation. Pharmacological inhibition of NFATc1 with cyclosporin A (CsA) abolished these effects, confirming NFATc1 as a central mediator of SFNMan-induced immune tolerance.
Conclusions And Implications:
Our findings identify NFATc1 as a key transcriptional switch in moDCs tolerogenic programming and highlight the carbohydrate-dependent specificity of SFN conjugates. SFNMan represents a novel carbohydrate-engineered immunomodulator capable of driving immune tolerance through NFATc1 activation. These results provide a mechanistic framework for the development of precision therapies targeting inflammatory and autoimmune diseases.
