Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis

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

Research output: Contribution to journalArticle

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 RORγwere 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 RORγmRNA. 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 RORγbut 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.

Original languageEnglish (US)
Article number44
JournalAllergy, Asthma and Clinical Immunology
Volume15
Issue number1
DOIs
StatePublished - Aug 1 2019
Externally publishedYes

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Interleukin-17
Rheumatoid Arthritis
Neutrophils
Interleukin-23
Th17 Cells
Interleukin-6
Cytokines
Serum

Keywords

  • DAS-28
  • IL-17
  • Neutrophils
  • Rheumatoid arthritis
  • Th17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

Cite this

Gonzalez Orozco, M., Barbosa-Cobos, R. E., Santana-Sanchez, P., Becerril-Mendoza, L., Limon-Camacho, L., Juarez-Estrada, A. I., ... Ortiz-Navarrete, V. (2019). Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis. Allergy, Asthma and Clinical Immunology, 15(1), [44]. https://doi.org/10.1186/s13223-019-0359-9

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.

In: Allergy, Asthma and Clinical Immunology, Vol. 15, No. 1, 44, 01.08.2019.

Research output: Contribution to journalArticle

Gonzalez Orozco, M, Barbosa-Cobos, RE, Santana-Sanchez, P, Becerril-Mendoza, L, Limon-Camacho, L, Juarez-Estrada, AI, Lugo-Zamudio, GE, Moreno-Rodriguez, J & Ortiz-Navarrete, V 2019, 'Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis', Allergy, Asthma and Clinical Immunology, vol. 15, no. 1, 44. https://doi.org/10.1186/s13223-019-0359-9
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. In: Allergy, Asthma and Clinical Immunology. 2019 ; Vol. 15, No. 1.
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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 RORγwere 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 RORγmRNA. 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 RORγbut 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.",
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T1 - Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis

AU - Gonzalez Orozco, Maria

AU - Barbosa-Cobos, Rosa E.

AU - Santana-Sanchez, Paola

AU - Becerril-Mendoza, Lizbeth

AU - Limon-Camacho, Leonardo

AU - Juarez-Estrada, Ana I.

AU - Lugo-Zamudio, Gustavo E.

AU - Moreno-Rodriguez, Jose

AU - Ortiz-Navarrete, Vianney

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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 RORγwere 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 RORγmRNA. 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 RORγbut 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.

AB - 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 RORγwere 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 RORγmRNA. 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 RORγbut 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.

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KW - Th17

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