Conformational changes in myeloperoxidase induced by ubiquitin and NETs containing free ISG15 from systemic lupus erythe
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rnal of Translational Medicine Open Access
RESEARCH
Conformational changes in myeloperoxidase induced by ubiquitin and NETs containing free ISG15 from systemic lupus erythematosus patients promote a pro‑inflammatory cytokine response in CD4+ T cells Daniel Alberto Carrillo‑Vázquez1,2,3, Eduardo Jardón‑Valadez4, Jiram Torres‑Ruiz2,5, Guillermo Juárez‑Vega6, José Luis Maravillas‑Montero6, David Eduardo Meza‑Sánchez6, María Lilia Domínguez‑López3, Jorge Carlos Alcocer Varela2 and Diana Gómez‑Martín2,6*
Abstract Background: Neutrophil extracellular traps (NETs) from patients with systemic lupus erythematosus (SLE) are charac‑ terized by lower ubiquitylation and myeloperoxidase (MPO) as a substrate. The structural and functional effect of such modification and if there are additional post-translational modifications (PTMs) are unknown. Methods: To assess the expression and functional role of PTMs in NETs of patients with SLE; reactivation, proliferation and cytokine production was evaluated by flow cytometry using co-cultures with dendritic cells (DC) and CD4+ from SLE patients and healthy controls. The impact of ubiquitylation on MPO was assessed by molecular dynamics. The expression of ISG15 in NETs was evaluated by immunofluorescence and Western Blot. Results: Fifteen patients with SLE and ten healthy controls were included. In the co-cultures of C D4+ lymphocytes with DC stimulated with ubiquitylated MPO or recombinant MPO, a higher expression of IFNγ and IL-17A was found in CD4+ from SLE patients (p
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