Dataset Information

Impaired Interleukin-18 Signaling in Natural Killer Cells From Patients With Systemic Juvenile Idiopathic Arthritis.

ABSTRACT:

Objective

Systemic juvenile idiopathic arthritis (sJIA) is characterized by fever, arthritis, rash, hepatosplenomegaly, and macrophage activation syndrome; however, its pathogenesis is still unclear. Elevated serum interleukin (IL)-18 concentrations and decreased natural killer (NK) cell activity are characteristic of active disease; thus, we examined IL-18 signaling in NK cells from sJIA.

Methods

We analyzed mitogen-activated protein kinase (MAPK) p38 and nuclear factor κ light chain enhancer of activated B cells (NFκB) p65 phosphorylation in NK cells after in vitro recombinant IL-18 (rIL-18) stimulation in 31 patients with sJIA. Associations between clinical features, serum IL-18, and phosphorylation intensity were analyzed. Furthermore, we investigated the effects of high IL-18 concentrations on phosphorylation in NK cells.

Results

Patients were divided according to their disease activity: systemic features (n = 8), chronic arthritis (n = 7), remission on medication (n = 10), and remission off medication (n = 6). MAPK p38 and NFκB p65 phosphorylation intensity were the highest in healthy controls, followed by remission off medication, remission on medication (vs. control; MAPK p38, P < 0.01; NFκB p65, P < 0.05), chronic arthritis (P < 0.001, P < 0.001), and systemic features (P < 0.001, P < 0.001). The systemic features group showed a complete defect in phosphorylation. Serum IL-18 was the highest in the systemic features group followed by chronic arthritis, remission on medication (P < 0.01), remission off medication (P < 0.01), and healthy controls (P < 0.01). Phosphorylation intensity was negatively correlated with serum IL-18 (MAPK p38, r² = 0.42; NFκB p65, r² = 0.54). Furthermore, healthy control NK cells were cultured with rIL-18; impaired phosphorylation was reproduced in vitro.

Conclusion

Impaired IL-18 signaling in NK cells correlated with disease activity in sJIA. High serum IL-18 exposure induces impaired MAPK and NFκB phosphorylation in NK cells.

SUBMITTER: Ohya T

PROVIDER: S-EPMC9190221 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Impaired Interleukin-18 Signaling in Natural Killer Cells From Patients With Systemic Juvenile Idiopathic Arthritis.

Ohya Takashi T Nishimura Kenichi K Murase Ayako A Hattori Seira S Ohara Asami A Nozawa Tomo T Hara Ryoki R Ito Shuichi S

ACR open rheumatology 20220311 6

<h4>Objective</h4>Systemic juvenile idiopathic arthritis (sJIA) is characterized by fever, arthritis, rash, hepatosplenomegaly, and macrophage activation syndrome; however, its pathogenesis is still unclear. Elevated serum interleukin (IL)-18 concentrations and decreased natural killer (NK) cell activity are characteristic of active disease; thus, we examined IL-18 signaling in NK cells from sJIA.<h4>Methods</h4>We analyzed mitogen-activated protein kinase (MAPK) p38 and nuclear factor κ light c ...[more]

PMID: 35275436

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Dataset Information

Impaired Interleukin-18 Signaling in Natural Killer Cells From Patients With Systemic Juvenile Idiopathic Arthritis.

Objective

Methods

Results

Conclusion

Publications

Impaired Interleukin-18 Signaling in Natural Killer Cells From Patients With Systemic Juvenile Idiopathic Arthritis.

Similar Datasets

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