Rheumatoid Synovial Fluids Regulate the Immunomodulatory Potential of Adipose-Derived Mesenchymal Stem Cells Through a TNF/NF-κB-Dependent Mechanism
| Autor: | Souraya Sayegh, Oula El Atat, Katy Diallo, Benjamin Rauwel, Yannick Degboé, Etienne Cavaignac, Arnaud Constantin, Alain Cantagrel, Viviane Trak-Smayra, Nada Alaaeddine, Jean-Luc Davignon |
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| Přispěvatelé: | Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Saint-Joseph de Beyrouth (USJ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Lebanese University [Beirut] (LU), CARBILLET, Véronique |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
rheumatoid arthritis TNF immunomodulation NF-κB Arthritis Rheumatoid 0302 clinical medicine synovial fluid MESH: Arthritis Rheumatoid / immunology [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Immunology and Allergy Medicine Original Research MESH: Adipose Tissue / cytology MESH: Middle Aged biology Cell adhesion molecule MESH: Infant Newborn MESH: Tumor Necrosis Factor-alpha / immunology NF-kappa B FOXP3 Middle Aged MESH: Infant MESH: Macrophages / immunology Adipose Tissue MESH: NF-kappa B / immunology Child Preschool [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases Tumor necrosis factor alpha lcsh:Immunologic diseases. Allergy Adult MESH: Synovial Fluid / immunology Immunology MESH: Immunomodulation Tregs 03 medical and health sciences MESH: Child Preschool Synovial fluid Humans Aged mesenchymal stem cells MESH: Humans CD40 business.industry Tumor Necrosis Factor-alpha Macrophages Mesenchymal stem cell Infant Newborn Correction Infant MESH: Mesenchymal Stem Cells / immunology MESH: Adult NFKB1 MESH: Adipose Tissue / immunology 030104 developmental biology Cancer research biology.protein business lcsh:RC581-607 CD80 030215 immunology |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology, 2019, 10, pp.1482. ⟨10.3389/fimmu.2019.01482⟩ |
| ISSN: | 1664-3224 |
| Popis: | International audience; Introduction: Adipose-derived mesenchymal stem cells (ADSC) have been shown to have remarkable immune-modulating effects. However, their efficacy in clinical trials has yet to be fully demonstrated. This could be due to a lack of a proper inflammatory environment in vivo that primes ADSC. Here, we define how the articular microenvironment of rheumatoid arthritis (RA) patients modulates the therapeutic efficiency of ADSC. Methods: Synovial fluids (SF) were collected from 8 RA patients, 2 Spondyloarthritis patients and one control synovial fluid from a patient undergoing traumatic-related surgery. SF inflammatory status was determined by routine analysis and quantification of pro-inflammatory cytokines. ADSC were first treated with SF and ADSC proliferation and gene expression of immunomodulatory factors was evaluated. In order to determine the mechanisms underlying the effect of SF on ADSC, tumor necrosis factor (TNF), interleukin-6 (IL-6), and NF-κB neutralization assays were performed. To evaluate the effect of SF on ADSC functions, ADSC were pre-treated with SF and then co-cultured with either macrophages or T cells. The modulation of their phenotype was assessed by flow cytometry. Results: Pro-inflammatory RASF maintained the proliferative capacity of ADSC and upregulated the gene expression of cyclooxygenase-2 (COX2), indoleamine-1,2-dioxygenase (IDO), interleukin-6 (IL-6), tumor-necrosis factor stimulated gene 6 (TSG6), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and programmed death-ligand 1 (PD-L1), all factors involved in ADSC immunomodulatory potential. The RASF-induced gene expression was mainly mediated by TNF alone or in combination with IL-6 and signaled through the NF-κB pathway. Conditioning ADSC with pro-inflammatory RASF enhanced their ability to induce CD4+Foxp3+CD25high regulatory T cells (Tregs) and inhibit pro-inflammatory markers CD40 and CD80 in activated macrophages. Conclusions: Inflammatory synovial fluids from RA patients had the capacity to modulate ADSC response, to induce Tregs and modulate the phenotype of macrophages. The clinical use of ADSC in affected joints should take into account the influence of the local articular environment on their potential. Having a sufficient pro-inflammatory microenvironment will determine whether optimal immunoregulatory response should be expected. Direct ADSC intra-articular delivery to patients could be a potential strategy to properly prime their immunomodulatory potential and enhance their clinical benefits. |
| Databáze: | OpenAIRE |
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