Academic Journal
The immunoregulatory effect of the TREM2-agonist Sulfavant A in human allogeneic mixed lymphocyte reaction
| العنوان: | The immunoregulatory effect of the TREM2-agonist Sulfavant A in human allogeneic mixed lymphocyte reaction |
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| المؤلفون: | Barra, Giusi, Gallo, Carmela, Carbone, Dalila, Ziaco, Marcello, Dell’Isola, Mario, Affuso, Mario, Manzo, Emiliano, Nuzzo, Genoveffa, Fioretto, Laura, D’Ippolito, Giuliana, De Palma, Raffaele, Fontana, Angelo |
| المساهمون: | Barra, Giusi, Gallo, Carmela, Carbone, Dalila, Ziaco, Marcello, Dell’Isola, Mario, Affuso, Mario, Manzo, Emiliano, Nuzzo, Genoveffa, Fioretto, Laura, D’Ippolito, Giuliana, De Palma, Raffaele, Fontana, Angelo |
| سنة النشر: | 2023 |
| المجموعة: | IRIS Università degli Studi di Napoli Federico II |
| مصطلحات موضوعية: | cancer immunotherapy, dendritic cell, drug discovery, homeostasi, immunoregulation, inflammation, small molecule, vaccine adjuvant |
| الوصف: | Introduction: Sulfavant A (SULF A) is a synthetic derivative of naturally occurring sulfolipids. The molecule triggers TREM2-related maturation of dendritic cells (DCs) and has shown promising adjuvant activity in a cancer vaccine model. Methods: the immunomodulatory activity of SULF A is tested in an allogeneic mixed lymphocyte reaction (MLR) assay based on monocyte-derived dendritic cells and naïve T lymphocytes from human donors. Flow cytometry multiparametric analyses and ELISA assays were performed to characterize the immune populations, T cell proliferation, and to quantify key cytokines. Results: Supplementation of 10 μg/mL SULF A to the co-cultures induced DCs to expose the costimulatory molecules ICOSL and OX40L and to reduce release of the pro-inflammatory cytokine IL-12. After 7 days of SULF A treatment, T lymphocytes proliferated more and showed increased IL-4 synthesis along with downregulation of Th1 signals such as IFNγ, T-bet and CXCR3. Consistent with these findings, naïve T cells polarized toward a regulatory phenotype with up-regulation of FOXP3 expression and IL-10 synthesis. Flow cytometry analysis also supported the priming of a CD127-/CD4+/CD25+ subpopulation positive for ICOS, the inhibitory molecule CTLA-4, and the activation marker CD69. Discussion: These results prove that SULF A can modulate DC-T cell synapse and stimulate lymphocyte proliferation and activation. In the hyperresponsive and uncontrolled context of the allogeneic MLR, the effect is associated to differentiation of regulatory T cell subsets and dampening of inflammatory signals. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000939909300001; volume:14; firstpage:1050113; journal:FRONTIERS IN IMMUNOLOGY; https://hdl.handle.net/11588/955957; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85149319243 |
| DOI: | 10.3389/fimmu.2023.1050113 |
| الاتاحة: | https://hdl.handle.net/11588/955957 https://doi.org/10.3389/fimmu.2023.1050113 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.3C7B1A73 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2023.1050113 |
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