Characterization of TLR4-mediated auto-antibody production in a mouse model of histidyl-tRNA synthetase-induced myositis:

Innate Immunity

LisaHarlow¹ 

关键词: TLR4;    MyD88;    TRIF;    histidyl-tRNA synthetase;    autoantibody;    classs witching;   

DOI  :  10.1177/1753425912446714

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

We have previously shown that intramuscular immunization with a recombinant fragment of murine histidyl-tRNA synthetase (HRS) in the absence of exogenous adjuvant generates Ag-specific, IgG class switched Abs a murine model of myositis. Markedly diminished IgG anti-HRS auto-Ab responses in TLR4 signaling-deficient C3H/HeJ mice indicate that TLR4 is required for auto-Ab formation and/or class switching in this system. Comparative time course assessment of HRS-immunized C3H/HeOuJ (wild type) and C3H/HeJ (TLR4 mutant) mice shows here that despite significant impairment of class switched IgG anti-HRS responses in TLR4-deficient C3H/HeJ mice, production of IgM anti-HRS auto-Abs is relatively preserved—suggesting that TLR4-mediated signals modulate IgG class switching rather than auto-Ab formation in this genetic background. In C57BL/6-derived knockout mice lacking either MyD88 (B6.MyD88−/−) or TRIF (B6.TRIF−/−) adaptor molecules, immunization studies indicate that TRIF exerts a dominant role in the generation ...

【 授权许可】

CC BY