Type I interferon therapy and its role in autoimmunity
Type I interferon therapy and its role in autoimmunity
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DOI：
10.3109/08916930903510971
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发表时间：
2010-04-01
期刊：
影响因子：
3.5
通讯作者：
Meroni, Pier Luigi
中科院分区：
文献类型：
--
作者：
Biggioggero, Martina;Gabbriellini, Lisa;Meroni, Pier Luigi
干扰素（ifn）对先天免疫和适应性免疫的不同细胞类型具有多效性，能够影响免疫应答。IFN，特别是I型IFN，激活树突状细胞和调节主要组织相容性I类和II类分子表达的能力也支持它们在耐受性的发展和维持中的潜在作用。当发生耐受性破坏时，核抗原与特异性自身抗体反应产生的免疫复合物可进一步诱导I型IFN的产生。因此，高酸不稳定的I型IFN血浆水平、IFN α诱导转录物的过度表达以及与I型IFN反应密切相关的基因的关联，代表了系统性红斑狼疮（一种典型的自身免疫性疾病）中所谓的IFN信号的基本原理。ifn对靶组织的直接和有害影响进一步支持了其在自身免疫中的作用。干扰素的治疗用途是基于它们的抗病毒和抗增殖作用。尤其是I型干扰素的使用，与自身免疫的出现有关，尽管频率低于预期。这种事件主要发生在既往有自身免疫表现的患者中，其特征可以是仅出现自身抗体或临床显性疾病。停止干扰素治疗通常（但并非总是）是控制自身免疫性疾病所必需的。
Interferons (IFNs) display a pleiotropic effect on different cell types of both the innate and the adaptive immunities being able to affect the immune responses. The ability of IFNs, and in particular of type I IFN, to activate dendritic cells and to modulate the expression of major histocompatibility classes I and II molecules supports their potential role also in the development and maintenance of tolerance. When tolerance breakdown has occurred, immunocomplexes generated by the reaction of nuclear antigens and specific autoantibodies can further induce type I IFN production. Accordingly, high acid-labile type I IFN plasma levels, overexpression of IFN alpha-induced transcripts and the association with genes closely related to type I IFN response represent the rationale for the so-called IFN signature in systemic lupus erythematosus, a prototypical autoimmune disease. The role of IFNs in autoimmunity is further supported by their direct and deleterious impact on target tissues. The therapeutic use of IFNs is based on their antiviral and antiproliferative effect. Type I IFN administration, in particular, is associated with the appearance of autoimmunity, although less frequently than expected. Such an event takes place mostly in patients with previous autoimmune manifestations and can be characterized by the appearance of autoantibodies only or of a clinically overt disease. IFN therapy cessation is usually, but not always, required for controlling the autoimmune disorders.