免疫系统受到高度调节,但是当失调时,次优的保护性免疫反应或过于强烈的免疫反应可导致免疫介导的疾病.免疫调节的遗传和分子机制尚未完全了解,阻碍更精确的诊断和治疗免疫介导的疾病的发展。最近,由小的开放阅读框编码的成千上万个以前未被识别的非规范微蛋白基因已经被鉴定出来。许多这些微蛋白执行关键功能,通常以特定于细胞和上下文的方式。现在已知几种微蛋白可以调节免疫力;然而,绝大多数是没有特色的。因此,照亮通常被称为“黑暗蛋白质组”的东西,“可能会提供更精确地调整免疫反应的机会。这里,我们回顾了非规范微蛋白生物学,强调最近发现的调节免疫力的例子,并讨论了通过靶向微蛋白来调节失调的免疫反应的潜力和挑战。
The immune system is highly regulated but, when dysregulated, suboptimal protective or overly robust immune responses can lead to immune-mediated disorders. The genetic and molecular mechanisms of immune regulation are incompletely understood, impeding the development of more precise diagnostics and therapeutics for immune-mediated disorders. Recently, thousands of previously unrecognized noncanonical
microprotein genes encoded by small open reading frames have been identified. Many of these microproteins perform critical functions, often in a cell- and context-specific manner. Several microproteins are now known to regulate immunity; however, the vast majority are uncharacterized. Therefore, illuminating what is often referred to as the \"dark proteome,\" may present opportunities to tune immune responses more precisely. Here, we review noncanonical
microprotein biology, highlight recently discovered examples regulating immunity, and discuss the potential and challenges of modulating dysregulated immune responses by targeting microproteins.