Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Allergy, Asthma & Clinical Immunology |
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| Online Access: | http://link.springer.com/article/10.1186/s13223-019-0359-9 |
| _version_ | 1818369365289992192 |
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| author | Maria Gonzalez-Orozco Rosa E. Barbosa-Cobos Paola Santana-Sanchez Lizbeth Becerril-Mendoza Leonardo Limon-Camacho Ana I. Juarez-Estrada Gustavo E. Lugo-Zamudio Jose Moreno-Rodriguez Vianney Ortiz-Navarrete |
| author_facet | Maria Gonzalez-Orozco Rosa E. Barbosa-Cobos Paola Santana-Sanchez Lizbeth Becerril-Mendoza Leonardo Limon-Camacho Ana I. Juarez-Estrada Gustavo E. Lugo-Zamudio Jose Moreno-Rodriguez Vianney Ortiz-Navarrete |
| author_sort | Maria Gonzalez-Orozco |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T23:22:41Z |
| format | Article |
| id | doaj.art-674593c7831042a3869c21517e3691b0 |
| institution | Directory Open Access Journal |
| issn | 1710-1492 |
| language | English |
| last_indexed | 2024-12-13T23:22:41Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Allergy, Asthma & Clinical Immunology |
| spelling | doaj.art-674593c7831042a3869c21517e3691b02022-12-21T23:27:40ZengBMCAllergy, Asthma & Clinical Immunology1710-14922019-08-0115111110.1186/s13223-019-0359-9Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritisMaria Gonzalez-Orozco0Rosa E. Barbosa-Cobos1Paola Santana-Sanchez2Lizbeth Becerril-Mendoza3Leonardo Limon-Camacho4Ana I. Juarez-Estrada5Gustavo E. Lugo-Zamudio6Jose Moreno-Rodriguez7Vianney Ortiz-Navarrete8Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalServicio de Reumatología, Hospital Juarez de MexicoDepartamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalServicio de Reumatología, Hospital Juarez de MexicoServicio de Reumatología, Hospital Central Norte, PemexDepartamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalServicio de Reumatología, Hospital Juarez de MexicoDireccion de Enseñanza e Investigacion, Hospital Juarez de MexicoDepartamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalAbstract 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.http://link.springer.com/article/10.1186/s13223-019-0359-9Rheumatoid arthritisNeutrophilsIL-17DAS-28Th17 |
| spellingShingle | Maria Gonzalez-Orozco Rosa E. Barbosa-Cobos Paola Santana-Sanchez Lizbeth Becerril-Mendoza Leonardo Limon-Camacho Ana I. Juarez-Estrada Gustavo E. Lugo-Zamudio Jose Moreno-Rodriguez Vianney Ortiz-Navarrete Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis Allergy, Asthma & Clinical Immunology Rheumatoid arthritis Neutrophils IL-17 DAS-28 Th17 |
| 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 | Rheumatoid arthritis Neutrophils IL-17 DAS-28 Th17 |
| url | http://link.springer.com/article/10.1186/s13223-019-0359-9 |
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