دورية أكاديمية
Low-density granulocytes activate T cells and demonstrate a non-suppressive role in systemic lupus erythematosus.
| العنوان: | Low-density granulocytes activate T cells and demonstrate a non-suppressive role in systemic lupus erythematosus. |
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| المؤلفون: | Rahman S; Department of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA., Sagar D; Department of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA., Hanna RN; Department of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA., Lightfoot YL; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA., Mistry P; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA., Smith CK; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA., Manna Z; Lupus Clinical Research Program, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA., Hasni S; Lupus Clinical Research Program, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA., Siegel RM; Immunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA., Sanjuan MA; Department of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA., Kolbeck R; Department of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA., Kaplan MJ; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA kerry.casey@alleninstitute.org mariana.kaplan@nih.gov., Casey KA; Department of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA kerry.casey@alleninstitute.org mariana.kaplan@nih.gov. |
| المصدر: | Annals of the rheumatic diseases [Ann Rheum Dis] 2019 Jul; Vol. 78 (7), pp. 957-966. Date of Electronic Publication: 2019 Apr 30. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BMJ Country of Publication: England NLM ID: 0372355 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-2060 (Electronic) Linking ISSN: 00034967 NLM ISO Abbreviation: Ann Rheum Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : BMJ Original Publication: London : H.K. Lewis |
| مواضيع طبية MeSH: | CD4-Positive T-Lymphocytes/*immunology , Granulocytes/*immunology , Lupus Erythematosus, Systemic/*immunology , Neutrophils/*immunology, Adolescent ; Adult ; Aged ; Case-Control Studies ; Cell Proliferation ; Female ; Flow Cytometry ; Humans ; Immunophenotyping ; Lupus Erythematosus, Systemic/blood ; Lymphocyte Activation ; Male ; Middle Aged ; Phenotype ; Young Adult |
| مستخلص: | Objectives: The presence of proinflammatory low-density granulocytes (LDG) has been demonstrated in autoimmune and infectious diseases. Recently, regulatory neutrophilic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) were identified in systemic lupus erythematosus (SLE). Because LDG and PMN-MDSC share a similar phenotype with contrasting functional effects, we explored these cells in a cohort of patients with SLE. Methods: LDG and normal-density granulocytes (NDG) were isolated from fresh blood of healthy donors (HD) and patients with SLE. Associations between LDG and clinical manifestations were analysed. Multicolor flow cytometry and confocal imaging were performed to immunophenotype the cells. The ability of LDG and NDG to suppress T cell function and induce cytokine production was quantified. Results: LDG prevalence was elevated in SLE versus HD, associated with the interferon (IFN) 21-gene signature and disease activity. Also, the LDG-to-lymphocyte ratio associated better with SLE disease activity index than neutrophil-to-lymphocyte ratio. SLE LDG exhibited significantly heightened surface expression of various activation markers and also of lectin-like oxidised low-density lipoprotein receptor-1, previously described to be associated with PMN-MDSC. Supernatants from SLE LDG did not restrict HD CD4 + T cell proliferation in an arginase-dependent manner, suggesting LDG are not immunosuppressive. SLE LDG supernatants induced proinflammatory cytokine production (IFN gamma, tumour necrosis factor alpha and lymphotoxin alpha) from CD4 + T cells. Conclusions: Based on our results, SLE LDG display an activated phenotype, exert proinflammatory effects on T cells and do not exhibit MDSC function. These results support the concept that LDG represent a distinct proinflammatory subset in SLE with pathogenic potential, at least in part, through their ability to activate type 1 helper responses. Competing Interests: Competing interests: SR, RNH and RK are employees at MedImmune. DS, MAS and KAC were employees at MedImmune during the time work was performed on this study. Other authors have nothing to declare. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) |
| التعليقات: | Comment in: Ann Rheum Dis. 2020 Oct;79(10):e135. (PMID: 31177097) Comment in: Ann Rheum Dis. 2020 Oct;79(10):e136. (PMID: 31272942) |
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| فهرسة مساهمة: | Keywords: T cells; autoimmune diseases; systemic lupus erythematosus |
| تواريخ الأحداث: | Date Created: 20190502 Date Completed: 20200304 Latest Revision: 20200304 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6585283 |
| DOI: | 10.1136/annrheumdis-2018-214620 |
| PMID: | 31040119 |
| قاعدة البيانات: | MEDLINE |
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