Characterization of Il-17Aa and Il-17Ff in Rheumatoid Arthritis and Multiple Sclerosis

Schofield, Cheryl; Fischer, Saloumeh K; Townsend, Michael J.; Mosesova, Sofia; Peng, Kun; Setiadi, A. Francesca; Song, An; Baruch, Amos

doi:10.4155/bio-2016-0207

Cited by 29 publications

(22 citation statements)

References 27 publications

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“…In summary, in line with prior data from other models, our data show that in resistant C57BL/6 mice, IL‐17A and IL‐17F are co‐produced by γδ T cells and CD4 + T cells. Secretion of IL‐17A and IL‐17F does not influence disease progression and parasite burdens in low dose infections with L. major .…”

Section: Discussionsupporting

confidence: 89%

“…IL‐17 is a proinflammatory cytokine secreted by CD4 + Th17 and γδ T cells as well as a subset of innate lymphoid cells (ILC3) . The main function of IL‐17 is to induce the production of various cytokines, for example, IL‐1 and TNFα, and chemokines leading to the recruitment of neutrophils and monocytes to sites of T‐cell activation . IL‐17 plays an important role in various diseases, for example, rheumatoid arthritis, psoriasis, multiple sclerosis and in defence mechanisms against extracellular microorganisms …”

Section: Introductionmentioning

confidence: 99%

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IL‐17A/F in Leishmania major‐resistant C57BL/6 mice

Dietze-Schwonberg

Kostka

Lorenz

et al. 2019

Experimental Dermatology

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Proinflammatory IL‐17 plays an important role in various diseases and defence against extracellular microorganisms. Healing of leishmaniasis is promoted by Th1/Tc1 cells, whereas Th2/Treg are associated with worsened disease outcome. In addition, high expression of IL‐17A in Leishmania‐susceptible BALB/c and artificial overexpression of IL‐17A in T cells in resistant C57BL/6 mice worsened disease outcome. Since C57BL/6 mice lacking only IL‐17A exhibited no phenotype, and IL‐17A and IL‐17F share similar receptors, but differentially regulate chemokine secretion, we studied mice lacking both IL‐17A and IL‐17F (IL‐17A/F−/−) in infections with Leishmania major. Interestingly, lesion volumes and parasite burdens were comparable to controls, IL‐17A/F−/− mice developed a Th1/Tc1 phenotype, and exhibited normal lesion resolution. Thus, in C57BL/6 mice, secretion of IL‐17A and IL‐17F does not influence disease progression. It appears that—depending on the genetic background—cytokines of the IL‐17 family might be responsible for disease progression primarily in susceptible mice.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

IL‐17A/F in Leishmania major‐resistant C57BL/6 mice

Dietze-Schwonberg

Kostka

Lorenz

et al. 2019

Experimental Dermatology

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“…Women. Circulating levels of IL-17A were undetectable in all samples from the series of premenopausal women, similar to what previously reported [15,16]. At variance, plasma levels of IL-17A were measurable in most PHPT and non-PHPT osteoporotic postmenopausal women.…”

Section: Circulating Il-17a Levels In Postmenopausal Phptsupporting

confidence: 88%

Circulating IL-17A Levels in Postmenopausal Women with Primary Hyperparathyroidism

Dozio

Passeri

Vianello

et al. 2020

Mediators of Inflammation

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Background. Primary hyperparathyroidism (PHPT) is a common cause of secondary osteoporosis in postmenopausal women. Th17 lymphocytes and the released cytokine IL-17A play an important role in bone metabolism. Th17 cells have been shown to be activated by PTH, and peripheral blood T cells from patients affected with PHPT express higher levels of IL-17A mRNA than controls. Aim. To investigate circulating levels of IL-17A and the ratio RANKL/OPG, as markers of osteoclastogenesis, in 50 postmenopausal PHPT women compared with postmenopausal osteoporotic non-PHPT women (n=20). Results. Circulating levels of IL-17A were similarly detectable in most PHPT and non-PHPT osteoporotic women (12.9 (8.4-23.1) vs. 11.3 (8.3-14.3) pg/ml, median (range interquartile), P=0.759), at variance with premenopausal women where IL-17A was undetectable. In PHPT women, any significant correlations could be detected between circulating IL-17A levels and PTH levels. Nonetheless, significant negative correlations between circulating IL-17A and ionized calcium levels (r=‐0.294, P=0.047) and urine calcium excretions (r=‐0.300, P=0.045) were found. Moreover, PHPT women were characterized by positive correlations between IL-17A levels and femur neck (r=0.364, P=0.021) and total hip (r=0.353, P=0.015) T-scores. Circulating IL-17A levels did not show any significant correlation with sRANKL, OPG, and sRANKL/OPG ratio in PHPT women. Conclusions. In postmenopausal PHPT women, circulating IL-17A levels were similar to those detected in postmenopausal non-PHPT women, showing a disruption of the relationship observed in postmenopausal osteoporosis among circulating PTH, sRANKL, OPG, IL-17A, and bone demineralization in postmenopausal PHPT women. The data support an osteogenic effect of IL-17A in postmenopausal PHPT women.

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“…Human IL-17A and IL-17F levels were quantified using the Singulex platform (Singulex, Alameda, CA) as previously described (Schofield et al, 2016). Pro-inflammatory cytokines and chemokines were quantified using a combination of electrochemiluminescence and multiarray technology (McKay et al, 2017).…”

Section: Rrms Patient Samples and Quantification Of Protein Levels Inmentioning

confidence: 99%

“…Levels of IL-17A and F in the CSF from RRMS patients and healthy donors (HD) were assessed with an immunoassay that resolved IL-17A and IL-17F isoforms (Schofield et al, 2016). IL-17A was detectable in the CSF in 38/50 (76%) RRMS patients and in 7/20 (35%) HD.…”

Section: Elevated Il-17a In the Csf From Rrms Patients Correlated Witmentioning

confidence: 99%

IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis

Setiadi¹,

Abbas²,

Jeet³

et al. 2019

Journal of Neuroimmunology

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A B S T R A C TIL-17 has been implicated in the pathogenesis of multiple sclerosis (MS). Here, we show that blockade of IL-17A, but not IL-17F, attenuated experimental autoimmune encephalomyelitis (EAE). We further show that IL-17A levels were elevated in the CSF of relapsing-remitting MS (RRMS) patients and that they correlated with the CSF/ serum albumin quotient (Qalb), a measure of blood-brain barrier (BBB) dysfunction. We then demonstrated that the combination of IL-17A and IL-6 reduced the expression of tight junction (TJ)-associated genes and disrupted monolayer integrity in the BBB cell line hCMEC/D3. However, unlike IL-17A, IL-6 in the CSF from RRMS patients did not correlate with Qalb. These data highlight the potential importance of targeting IL-17A in preserving BBB integrity in RRMS.

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Characterization of Il-17Aa and Il-17Ff in Rheumatoid Arthritis and Multiple Sclerosis

Abstract: Reliable determination of IL-17 isoforms in the systemic and CNS compartments sheds light on the involvement of IL-17AA and IL-17FF in autoimmunity.

Cited by 29 publications

References 27 publications

IL‐17A/F in Leishmania major‐resistant C57BL/6 mice

IL‐17A/F in Leishmania major‐resistant C57BL/6 mice

Circulating IL-17A Levels in Postmenopausal Women with Primary Hyperparathyroidism

IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis

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