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Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis
BACKGROUND: Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA). It has recently been reported that in addition to T helper (Th) 17 cells, other cells, including neutrophils, produce IL-17A, an important inflammatory cytokine involved in the pathogenesis of RA. The pu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676628/ https://www.ncbi.nlm.nih.gov/pubmed/31388340 http://dx.doi.org/10.1186/s13223-019-0359-9 |
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author | Gonzalez-Orozco, Maria Barbosa-Cobos, Rosa E. Santana-Sanchez, Paola Becerril-Mendoza, Lizbeth Limon-Camacho, Leonardo Juarez-Estrada, Ana I. Lugo-Zamudio, Gustavo E. Moreno-Rodriguez, Jose Ortiz-Navarrete, Vianney |
author_facet | Gonzalez-Orozco, Maria Barbosa-Cobos, Rosa E. Santana-Sanchez, Paola Becerril-Mendoza, Lizbeth Limon-Camacho, Leonardo Juarez-Estrada, Ana I. Lugo-Zamudio, Gustavo E. Moreno-Rodriguez, Jose Ortiz-Navarrete, Vianney |
author_sort | Gonzalez-Orozco, Maria |
collection | PubMed |
description | BACKGROUND: Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA). It has recently been reported that in addition to T helper (Th) 17 cells, other cells, including neutrophils, produce IL-17A, an important inflammatory cytokine involved in the pathogenesis of RA. The purpose of this study was to examine the presence of interleukin 17A-producing neutrophils in patients with RA. METHODS: We performed a cross-sectional study including 106 patients with RA and 56 healthy individuals. Whole peripheral blood cells were analyzed by flow cytometry to identify CD66b+ CD177+ IL-17A+ neutrophils and CD3+ CD4+ IL-17A+ T cells. Serum levels of IL-17A and IL-6 were measured by means of cytometry bead array (CBA). In purified neutrophils, mRNA levels of IL-17 and RORγ were measured by RT-PCR. In addition, purified neutrophils from patients and healthy controls were stimulated with the cytokines IL-6 and IL-23 to evaluate differences in their capacity to produce IL-17A. RESULTS: Neutrophils from RA patients expressed IL-17 and RORγ mRNA. Consequently, these cells also expressed IL-17A. Serum IL-17A levels but not Th17 cell numbers were increased in RA patients. Neutrophils positive for cytoplasmic IL-17A were more abundant in patients with RA (mean 1.2 ± 3.18%) than in healthy individuals (mean 0.07 ± 0.1%) (p < 0.0001). Although increased IL-17A+ neutrophil numbers were present in RA patients regardless of disease activity (mean 6.5 ± 5.14%), they were more frequent in patients with a more recent diagnosis (mean time after disease onset 3.5 ± 4.24 years). IL-6 and IL-23 induced the expression of RORγ but failed to induce IL-17A expression by neutrophils from RA patients and healthy individuals after a 3 h stimulation. CONCLUSION: IL-17A-producing neutrophils are increased in some RA patients, which are not related to disease activity but have an increased frequency in patients with recent-onset disease. This finding suggests that IL-17A-producing neutrophils play an early role in the development of RA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13223-019-0359-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6676628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66766282019-08-06 Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis Gonzalez-Orozco, Maria Barbosa-Cobos, Rosa E. Santana-Sanchez, Paola Becerril-Mendoza, Lizbeth Limon-Camacho, Leonardo Juarez-Estrada, Ana I. Lugo-Zamudio, Gustavo E. Moreno-Rodriguez, Jose Ortiz-Navarrete, Vianney Allergy Asthma Clin Immunol Research BACKGROUND: Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA). It has recently been reported that in addition to T helper (Th) 17 cells, other cells, including neutrophils, produce IL-17A, an important inflammatory cytokine involved in the pathogenesis of RA. The purpose of this study was to examine the presence of interleukin 17A-producing neutrophils in patients with RA. METHODS: We performed a cross-sectional study including 106 patients with RA and 56 healthy individuals. Whole peripheral blood cells were analyzed by flow cytometry to identify CD66b+ CD177+ IL-17A+ neutrophils and CD3+ CD4+ IL-17A+ T cells. Serum levels of IL-17A and IL-6 were measured by means of cytometry bead array (CBA). In purified neutrophils, mRNA levels of IL-17 and RORγ were measured by RT-PCR. In addition, purified neutrophils from patients and healthy controls were stimulated with the cytokines IL-6 and IL-23 to evaluate differences in their capacity to produce IL-17A. RESULTS: Neutrophils from RA patients expressed IL-17 and RORγ mRNA. Consequently, these cells also expressed IL-17A. Serum IL-17A levels but not Th17 cell numbers were increased in RA patients. Neutrophils positive for cytoplasmic IL-17A were more abundant in patients with RA (mean 1.2 ± 3.18%) than in healthy individuals (mean 0.07 ± 0.1%) (p < 0.0001). Although increased IL-17A+ neutrophil numbers were present in RA patients regardless of disease activity (mean 6.5 ± 5.14%), they were more frequent in patients with a more recent diagnosis (mean time after disease onset 3.5 ± 4.24 years). IL-6 and IL-23 induced the expression of RORγ but failed to induce IL-17A expression by neutrophils from RA patients and healthy individuals after a 3 h stimulation. CONCLUSION: IL-17A-producing neutrophils are increased in some RA patients, which are not related to disease activity but have an increased frequency in patients with recent-onset disease. This finding suggests that IL-17A-producing neutrophils play an early role in the development of RA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13223-019-0359-9) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-01 /pmc/articles/PMC6676628/ /pubmed/31388340 http://dx.doi.org/10.1186/s13223-019-0359-9 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Gonzalez-Orozco, Maria Barbosa-Cobos, Rosa E. Santana-Sanchez, Paola Becerril-Mendoza, Lizbeth Limon-Camacho, Leonardo Juarez-Estrada, Ana I. Lugo-Zamudio, Gustavo E. Moreno-Rodriguez, Jose Ortiz-Navarrete, Vianney Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis |
title | Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis |
title_full | Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis |
title_fullStr | Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis |
title_full_unstemmed | Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis |
title_short | Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis |
title_sort | endogenous stimulation is responsible for the high frequency of il-17a-producing neutrophils in patients with rheumatoid arthritis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676628/ https://www.ncbi.nlm.nih.gov/pubmed/31388340 http://dx.doi.org/10.1186/s13223-019-0359-9 |
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