Low-density granulocytes activate T cells and demonstrate a non-suppressive role in systemic lupus erythematosus
| Autor: | Zerai Manna, Richard M. Siegel, Yaíma L. Lightfoot, Pragnesh Mistry, Kerry A. Casey, Carolyne K. Smith, Richard N. Hanna, Saifur Rahman, Divya Sagar, Mariana J. Kaplan, Roland Kolbeck, Sarfaraz Hasni, Miguel A. Sanjuan |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lymphotoxin alpha medicine.medical_treatment T cell Immunology T cells General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine Flow cytometry 03 medical and health sciences 0302 clinical medicine Immunophenotyping systemic lupus erythematosus Rheumatology immune system diseases Interferon Immunology and Allergy Medicine autoimmune diseases skin and connective tissue diseases medicine.diagnostic_test business.industry 3. Good health 030104 developmental biology Cytokine medicine.anatomical_structure business 030215 immunology Lipoprotein medicine.drug |
| Zdroj: | Annals of the Rheumatic Diseases |
| ISSN: | 1468-2060 0003-4967 |
| DOI: | 10.1136/annrheumdis-2018-214620 |
| Popis: | ObjectivesThe 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.MethodsLDG 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.ResultsLDG 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.ConclusionsBased 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. |
| Databáze: | OpenAIRE |
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