Ehlers Marc, Ravetch Jeffrey V
Laboratory of Tolerance and Autoimmunity, German Arthritis Research Center (DRFZ), D-10117 Berlin, Germany.
Trends Immunol. 2007 Feb;28(2):74-9. doi: 10.1016/j.it.2006.12.006. Epub 2007 Jan 2.
Toll-like receptor (TLR) activation by pathogens can induce the activation of diverse cell populations of the immune system and, therefore, can initiate or augment protective T-helper 1 immune responses. However, on a susceptible genetic background, TLR stimulation can also induce autoimmunity. The relative contribution of either microbe-derived or endogenous antigens, such as single-stranded RNA and unmethylated DNA, to TLR stimulation and the development of specific autoimmune diseases are still debated. Here, we review the different possibilities. Furthermore, tolerance induction by TLRs, which originally had been postulated to be protective by limiting excessive inflammation and, thus, preventing septic shock, has come into focus as a mechanism to control autoimmunity by inhibiting dendritic-cell maturation. In some murine models of systemic lupus erythematosus, TLR9 deficiency results in a shift from anti-nucleosome to TLR7-dependent anti-ribonucleoprotein IgG2a and IgG2b autoantibodies, and enhanced disease progression and mortality. Thus, not only can TLR signalling induce autoimmunity, but TLR(9) stimulation might also regulate tolerance.
病原体激活Toll样受体（TLR）可诱导免疫系统中多种细胞群体的激活，因此可启动或增强保护性辅助性T细胞1免疫反应。然而，在易感遗传背景下，TLR刺激也可诱导自身免疫。微生物来源的抗原或内源性抗原，如单链RNA和未甲基化DNA，对TLR刺激及特定自身免疫性疾病发展的相对贡献仍存在争议。在此，我们综述了不同的可能性。此外，TLR最初被认为通过限制过度炎症从而预防脓毒症休克来发挥保护作用，现在其诱导的耐受性作为一种通过抑制树突状细胞成熟来控制自身免疫的机制受到关注。在一些系统性红斑狼疮的小鼠模型中，TLR9缺陷导致抗核小体自身抗体向TLR7依赖性抗核糖核蛋白IgG2a和IgG2b自身抗体转变，并增强疾病进展和死亡率。因此，TLR信号传导不仅可诱导自身免疫，TLR（9）刺激也可能调节耐受性。
