1,25dihydroxyvitamin D3 curtails the inflammatory and T cell stimulatory capacity of macrophages through an IL-10-dependent mechanism
| Autor: | Tatiana Takiishi, Chantal Mathieu, Decio L. Eizirik, Benoit Stijlemans, Hannelie Korf, Mathias Wenes, Sofie Robert, Michela Miani, Conny Gysemans |
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| Přispěvatelé: | Department of Bio-engineering Sciences, Cellular and Molecular Immunology, Pathologic Biochemistry and Physiology, Metajuridica, Fundamental rights centre |
| Předmět: |
medicine.medical_specialty
Chemokine Macrophage type 1 diabetes T cell T-Lymphocytes Immunology Nitric Oxide Synthase Type II Biology Lymphocyte Activation Calcitriol receptor 03 medical and health sciences Mice 0302 clinical medicine Immune system Calcitriol Mice Inbred NOD Internal medicine medicine Immunology and Allergy CXCL10 Animals Vitamin D Cells Cultured 030304 developmental biology 0303 health sciences Interleukin-12 Subunit p40 Tumor Necrosis Factor-alpha Macrophages Hematology Cell biology Interleukin-10 Mice Inbred C57BL Interleukin 10 Disease Models Animal Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 1 inflammation biology.protein Receptors Calcitriol Tumor necrosis factor alpha Female Chemokines CXC 030217 neurology & neurosurgery |
| Zdroj: | Vrije Universiteit Brussel Immunobiology; Vol 217 |
| Popis: | The vitamin D receptor (VDR) is a hormone nuclear receptor regulating bone and calcium homeostasis. Studies revealing the expression of VDR on immune cells point toward a role for VDR-dependent signaling pathways in immunity. Here we verified the ability of the natural VDR ligand, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) to interfere in inflammatory and T cell stimulatory capacity of macrophages, in particular within a chronic inflammatory disease features of experimental type 1 diabetes (T1D). We demonstrated that VDR is constitutively expressed in macrophages and both the levels of VDR and its downstream targets, are clearly induced by 1,25(OH)(2)D(3). In control mice, macrophage programming with 1,25(OH)(2)D(3) partially abrogated the activation-provoked expression of IL-12p40, TNFα and iNOS as well as the effector T cell-recruiting chemokines, CXCL9, CXCL10 and CXCL11. Targeting VDR signaling in macrophages counteracted their T-cell stimulatory ability despite essentially unaltered expression of antigen-presenting and costimulatory molecules. Furthermore, even in non-obese diabetic (NOD) mice, where macrophages/monocytes featured a heightened responsiveness toward danger signals and a superior T cell stimulatory capacity, 1,25(OH)(2)D(3) successfully curtailed these basic macrophage-mediated functions. Interestingly, the inhibitory action of the active compound was associated with an IL-10-dependent mechanism since 1,25(OH)(2)D(3)-treatment of IL-10-deficient macrophages failed to reproduce the characteristic repression on inflammatory mediators or T cell proliferation. Combined, these results highlight the possible therapeutic applicability of this natural immunomodulator, due to its ability to counteract macrophage inflammatory and T cell-activating pathways. |
| Databáze: | OpenAIRE |
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