Carbamylation-dependent activation of T cells: a novel mechanism in the pathogenesis of autoimmune arthritis.
Carbamylation-dependent activation of T cells: a novel mechanism in the pathogenesis of autoimmune arthritis.
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DOI：
10.4049/jimmunol.1000075
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发表时间：
2010-06-15
期刊：
影响因子：
--
通讯作者：
Bokarewa M
中科院分区：
文献类型：
--
作者：
Mydel P;Wang Z;Brisslert M;Hellvard A;Dahlberg LE;Hazen SL;Bokarewa M
蛋白质的翻译后修饰具有产生新表位的潜力，所述新表位可随后触发免疫应答。赖氨酸残基氨甲酰化形成高瓜氨酸可能是引发炎症反应的关键机制。我们评估了氨甲酰化在引发免疫反应中的作用，并报告了这一过程在诱导关节炎中的新作用。用含高瓜氨酸的肽免疫小鼠诱导趋化性、T细胞活化和Ab产生。关节内注射高瓜氨酸和瓜氨酸衍生肽后，小鼠也发生了糜烂性关节炎。将高瓜氨酸免疫小鼠的T和B细胞连续转移到正常受体中可诱导关节炎，而全身注射高瓜氨酸特异性抗体或关节内注射高瓜氨酸抗体/瓜氨酸肽混合物则不会诱导关节炎。因此，T细胞对高瓜氨酸衍生肽的应答以及随后抗高瓜氨酸抗体的产生对于诱导针对瓜氨酸衍生肽的自身免疫反应至关重要，并为关节炎的发病机制提供了新的机制。
The posttranslational modification of proteins has the potential to generate neoepitopes that may subsequently trigger immune responses. The carbamylation of lysine residues to form homocitrulline may be a key mechanism triggering inflammatory responses. We evaluated the role of carbamylation in triggering immune responses and report a new role for this process in the induction of arthritis. Immunization of mice with homocitrulline-containing peptides induced chemotaxis, T cell activation, and Ab production. The mice also developed erosive arthritis following intra-articular injection of peptides derived from homocitrulline and citrulline. Adoptive transfer of T and B cells from homocitrulline-immunized mice into normal recipients induced arthritis, whereas systemic injection of homocitrulline-specific Abs or intra-articular injection of homocitrulline-Ab/citrulline-peptide mixture did not. Thus, the T cell response to homocitrulline-derived peptides, as well as the subsequent production of anti-homocitrulline Abs, is critical for the induction of autoimmune reactions against citrulline-derived peptides and provides a novel mechanism for the pathogenesis of arthritis.
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影响因子：
2.2
作者：
CZERKINSKY, CC;NILSSON, LA;TARKOWSKI, A
通讯作者：
TARKOWSKI, A
影响因子：
3.8
作者：
Cai, LP;Yin, JP;Filvaroff, EH
通讯作者：
Filvaroff, EH
影响因子：
4.1
作者：
BESWICK, HT;HARDING, JJ
通讯作者：
HARDING, JJ
影响因子：
4.6
作者：
Duplan, V.;Foulquier, C.;Sebbag, M.
通讯作者：
Sebbag, M.
影响因子：
3.7
作者：
Amu, S.;Gjertsson, I.;Brisslert, M.
通讯作者：
Brisslert, M.