دورية أكاديمية
Immune Complex-Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity.
| العنوان: | Immune Complex-Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity. |
|---|---|
| المؤلفون: | Dalby E; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742., Christensen SM; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742., Wang J; Department of Respiratory, Inflammation, and Autoimmunity, AstraZeneca, Gaithersburg, MD 20878., Hamidzadeh K; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742., Chandrasekaran P; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742., Hughitt VK; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.; Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742., Tafuri WL; Department of General Pathology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; and., Arantes RME; Department of General Pathology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; and., Rodrigues IA; Instituto Metropolitano de Ensino Superior, Ipatinga 35164-253, Brazil., Herbst R; Department of Respiratory, Inflammation, and Autoimmunity, AstraZeneca, Gaithersburg, MD 20878., El-Sayed NM; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.; Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742., Sims GP; Department of Respiratory, Inflammation, and Autoimmunity, AstraZeneca, Gaithersburg, MD 20878; simsg@medimmune.com dmosser@umd.edu., Mosser DM; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742; simsg@medimmune.com dmosser@umd.edu. |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2020 Jul 01; Vol. 205 (1), pp. 102-112. Date of Electronic Publication: 2020 May 20. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Antigen-Antibody Complex/*metabolism , Leprosy, Lepromatous/*immunology , Leprosy, Tuberculoid/*immunology , Macrophages/*immunology, Biopsy ; Cell Differentiation/immunology ; Cell Line ; Disease Progression ; Glycogen Synthase Kinase 3/antagonists & inhibitors ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Leprosy, Lepromatous/pathology ; Leprosy, Tuberculoid/pathology ; Macrophage Activation ; Macrophages/metabolism ; Male ; Middle Aged ; Neovascularization, Physiologic/immunology ; Proto-Oncogene Proteins c-akt/metabolism ; RNA-Seq ; Receptors, IgG/metabolism ; Signal Transduction/genetics ; Signal Transduction/immunology ; Skin/cytology ; Skin/immunology ; Skin/pathology ; Toll-Like Receptors/metabolism ; Young Adult |
| مستخلص: | To maintain homeostasis, macrophages must be capable of assuming either an inflammatory or an anti-inflammatory phenotype. To better understand the latter, we stimulated human macrophages in vitro with TLR ligands in the presence of high-density immune complexes (IC). This combination of stimuli resulted in a broad suppression of inflammatory mediators and an upregulation of molecules involved in tissue remodeling and angiogenesis. Transcriptomic analysis of TLR stimulation in the presence of IC predicted the downstream activation of AKT and the inhibition of GSK3. Consequently, we pretreated LPS-stimulated human macrophages with small molecule inhibitors of GSK3 to partially phenocopy the regulatory effects of stimulation in the presence of IC. The upregulation of DC-STAMP and matrix metalloproteases was observed on these cells and may represent potential biomarkers for this regulatory activation state. To demonstrate the presence of these anti-inflammatory, growth-promoting macrophages in a human infectious disease, biopsies from patients with leprosy (Hanseniasis) were analyzed. The lepromatous form of this disease is characterized by hypergammaglobulinemia and defective cell-mediated immunity. Lesions in lepromatous leprosy contained macrophages with a regulatory phenotype expressing higher levels of DC-STAMP and lower levels of IL-12, relative to macrophages in tuberculoid leprosy lesions. Therefore, we propose that increased signaling by FcγR cross-linking on TLR-stimulated macrophages can paradoxically promote the resolution of inflammation and initiate processes critical to tissue growth and repair. It can also contribute to infectious disease progression. (Copyright © 2020 by The American Association of Immunologists, Inc.) |
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| معلومات مُعتمدة: | R01 GM102589 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (Antigen-Antibody Complex) 0 (Receptors, IgG) 0 (Toll-Like Receptors) EC 2.7.11.1 (AKT1 protein, human) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) EC 2.7.11.26 (Glycogen Synthase Kinase 3) |
| تواريخ الأحداث: | Date Created: 20200522 Date Completed: 20210311 Latest Revision: 20220809 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9358719 |
| DOI: | 10.4049/jimmunol.1901382 |
| PMID: | 32434940 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
|---|---|
| DOI: | 10.4049/jimmunol.1901382 |