Polarization of Rheumatoid Macrophages by TNF Targeting Through an IL-10/STAT3 Mechanism
| Autor: | Yannick, Degboé, Benjamin, Rauwel, Michel, Baron, Jean-Frédéric, Boyer, Adeline, Ruyssen-Witrand, Arnaud, Constantin, 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CARBILLET, Véronique |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
STAT3 Transcription Factor MESH: Immunophenotyping Immunology TNF macrophage Immunophenotyping Arthritis Rheumatoid MESH: Leukocytes MESH: Arthritis Rheumatoid / therapy STAT3 MESH: STAT3 Transcription Factor / metabolism [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases alternative polarization Humans MESH: Tumor Necrosis Factor-alpha / antagonists & inhibitors MESH: Tumor Necrosis Factor-alpha / metabolism Cells Cultured Aged Original Research MESH: Aged MESH: Arthritis Rheumatoid / diagnosis MESH: Humans Tumor Necrosis Factor-alpha Gene Expression Profiling Macrophages MESH: Cytokines / metabolism Macrophage Activation Middle Aged Interleukin-10 MESH: Interleukin-10 / metabolism Leukocytes Mononuclear MESH: Biomarkers [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases Cytokines Female anti-TNF agents interleukin 10 MESH: Mononuclear / drug effects MESH: Macrophage Activation / immunology Biomarkers MESH: Cells Cultured |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, 2019, 10, 14 p. ⟨10.3389/fimmu.2019.00003⟩ |
| ISSN: | 1664-3224 |
| Popis: | International audience; Macrophages contribute to the pathogenesis of rheumatoid arthritis (RA). They can display different states of activation or "polarization," notably the so-called inflammatory "M1" and the various alternative "M2" polarizations, characterized by distinct functions. Data regarding the effects of RA anti-cytokine biological disease-modifying anti-rheumatic drugs (bDMARDs) on macrophage polarization are scarce. We aimed to assess in vitro modulation of macrophage polarization by bDMARDs targeting pro-inflammatory cytokines in RA. We generated monocyte derived macrophages using blood samples from 20 RA patients with active RA and 30 healthy controls. We evaluated in vitro the impact on M1 inflammatory macrophages of: etanercept (ETA), adalimumab (ADA), certolizumab (CZP), tocilizumab (TCZ), and rituximab (RTX). We assessed the impact on macrophage polarization using flow cytometry and RTqPCR to study the expression of surface markers and perform functional studies of cytokine production, phagocytosis, and negative feedback control of inflammation. Among evaluated bDMARDs, anti-TNF agents modulated the polarization of inflammatory macrophages by decreasing inflammatory surface markers (CD40, CD80) and favoring alternative markers (CD16, CD163, MerTK). Anti-TNF agents also induced alternative functions in macrophages activated in inflammatory condition with (i) the inhibition of inflammatory cytokines (TNF, IL-6, IL-12), (ii) an increase in phagocytosis. These findings were mechanistically related to an increase in early IL-10 production, responsible for higher negative feedback control of inflammation involving SOCS3 and Gas6. This IL-10 effect was STAT3-dependent. Anti-TNF agents not only inhibit in vitro inflammatory functions of macrophages, but also favor resolution of inflammation through polarization toward alternative features specifically involving the IL-10/STAT3 axis. |
| Databáze: | OpenAIRE |
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