瓜氨酸化
瓜氨酸
自身免疫
细胞外
中性粒细胞胞外陷阱
巨噬细胞
免疫学
关节炎
化学
炎症
抗体
细胞生物学
体外
医学
生物
生物化学
精氨酸
氨基酸
作者
Mohey Eldin El Shikh,Riham El Sayed,Alessandra Nerviani,Katriona Goldmann,Christopher R. John,Rebecca Hands,Liliane Fossati-Jimack,Myles Lewis,Costantino Pitzalis
标识
DOI:10.1016/j.jaut.2019.06.008
摘要
The mechanisms underlying the transition of rheumatoid arthritis (RA) systemic autoimmunity to the joints remain largely unknown. Here, we demonstrate that macrophages in the secondary lymphoid organs (SLOs) and synovial ectopic lymphoid-like structures (ELSs) express peptidylarginine deiminase 4 (PAD4) in murine collagen induced arthritis (CIA) and synovial biopsies from RA patients. Moreover, peptidyl citrulline colocalized with macrophages in SLOs and ELSs, and depletion of macrophages in CIA decreased lymphoid tissue citrullination and serum anti-citrullinated protein/peptide antibody (ACPA) levels. Furthermore, PAD was released from activated murine and RA synovial tissue and fluid (SF) macrophages which functionally deiminated extracellular proteins/peptides in vitro. Additionally, activated murine and SF macrophages displayed macrophage extracellular trap formation (METosis) and release of intracellular citrullinated histones. Moreover, presentation of citrullinated proteins induced ACPA production in vitro. Thus, lymphoid tissue macrophages contribute to self-antigen citrullination and ACPA production, indicating that their selective targeting would potentially ameliorate citrullination-dependent autoimmune disorders.
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