Choubey Divaker, Panchanathan Ravichandran
Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, P. O. Box-670056, Cincinnati, OH 45267, United States; Research Service, ML-151, Cincinnati VA Medical Center, 3200 Vine Street, Cincinnati, OH 45220, United States.
Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, P. O. Box-670056, Cincinnati, OH 45267, United States; Research Service, ML-151, Cincinnati VA Medical Center, 3200 Vine Street, Cincinnati, OH 45220, United States.
Clin Immunol. 2017 Mar;176:42-48. doi: 10.1016/j.clim.2016.12.011. Epub 2017 Jan 3.
Type I interferons (IFN-α/β)-inducible PYRIN and HIN domain-containing protein family includes Absent in Melanoma 2 (murine Aim2 and human AIM2), murine p202, and human PYRIN-only protein 3 (POP3). The generation of Aim2-deficient mice indicated that the Aim2 protein is essential for inflammasome activation, resulting in the secretion of interleukin-1β (IL-1β) and IL-18 and cell death by pyroptosis. Further, Aim2-deficiency also increased constitutive expression of the IFN-β and expression of the p202 protein. Notably, an increased expression of p202 protein in female mice associated with the development of systemic lupus erythematosus (SLE). SLE in patients is characterized by a constitutive increase in serum levels of IFN-α and an increase in the expression IFN-stimulated genes. Recent studies indicate that p202 and POP3 proteins inhibit activation of the Aim2/AIM2 inflammasome and promote IFN-β expression. Therefore, we discuss the role of Aim2/AIM2 proteins in the suppression of type I IFNs production and lupus susceptibility.
I型干扰素（IFN-α/β）诱导的含PYRIN和HIN结构域的蛋白家族包括黑色素瘤缺失蛋白2（小鼠的Aim2和人类的AIM2）、小鼠的p202以及人类仅含PYRIN的蛋白3（POP3）。Aim2基因敲除小鼠的产生表明，Aim2蛋白对于炎性小体激活至关重要，可导致白细胞介素-1β（IL-1β）和IL-18的分泌以及细胞焦亡引起的细胞死亡。此外，Aim2缺陷还增加了IFN-β的组成型表达以及p202蛋白的表达。值得注意的是，雌性小鼠中p202蛋白表达增加与系统性红斑狼疮（SLE）的发生有关。患者的SLE特征为血清IFN-α水平的组成型升高以及IFN刺激基因表达的增加。最近的研究表明，p202和POP3蛋白可抑制Aim2/AIM2炎性小体的激活并促进IFN-β的表达。因此，我们讨论了Aim2/AIM2蛋白在抑制I型干扰素产生和狼疮易感性中的作用。
