Combined immunodeficiencies due to defects in signal transduction:: Defects of the γc-JAK3 signaling pathway as a model
Combined immunodeficiencies due to defects in signal transduction:: Defects of the γc-JAK3 signaling pathway as a model
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DOI：
10.1016/s0171-2985(00)80058-3
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发表时间：
2000-08-01
期刊：
影响因子：
2.8
通讯作者：
Ugazio, AG
中科院分区：
文献类型：
--
作者：
Notarangelo, LD;Giliani, S;Ugazio, AG
联合免疫缺陷包括一系列以T和B淋巴细胞的发育或功能缺陷为特征的遗传性疾病。细胞生物学和分子遗传学的最新进展揭示了大多数这些缺陷的病理生理学。特别是，人类中最常见的严重联合免疫缺陷形式，缺乏循环T细胞，B淋巴细胞数量正常或增加，以及X连锁遗传模式（SCIDX 1），已被证明是由于IL 2 RG基因的缺陷，该基因编码由几种细胞因子受体共享的共同γ链（γ（c））。此外，在常染色体隐性T-B+ SCID患者中已发现JAK 3基因缺陷，该基因编码通过含γ（c）的细胞因子受体进行信号转导所需的细胞内酪氨酸激酶。通过对SCID患者的详细分析，对通过γ（c）-JAK 3信号传导途径发出信号的细胞因子的功能特性进行表征是有利的。具体地说，IL-7在促进T细胞发育中的关键作用已通过鉴定具有IL-7受体α亚单位缺陷的罕见T-B+ SCID患者得到证实（IL7R α）沿着可能导致联合免疫缺陷的相同信号传导途径的遗传缺陷的异质性被可能与相同免疫缺陷中的缺陷相关的免疫表型的异质性所掩盖。基因，从而创造了详细的免疫学和分子研究的需要，以剖析在人类的组合免疫缺陷的频谱。
Combined immune deficiencies comprise a spectrum of genetic disorders characterized by developmental or functional defects of both T and B lymphocytes. Recent progress in cell biology and molecular genetics has unraveled the pathophysiology of most of these defects. In particular, the most common form of severe combined immune deficiency in humans, with lack of circulating T cells, a normal or increased number of B lymphocytes, and an X-linked pattern of inheritance (SCIDX1) has been shown to be due to defects of the IL2RG gene, encoding for the common gamma chain (gamma(c)), shared by several cytokine receptors. Furthermore, defects of the JAK3 gene, encoding for an intracellular tyrosine kinase required for signal transduction through gamma(c)-containing cytokine receptors, have been identified in patients with autosomal recessive T-B+ SCID. Characterization of the functional properties of cytokines that signal through the gamma(c)-JAK3 signaling pathway has been favored by the detailed analysis of SCID patients. Specifically, the key role of IL-7 in promoting T cell development has been substantiated by the identification of rare patients with T-B+ SCID who have a defect in the alpha subunit of the IL-7 receptor (IL7R alpha).The heterogeneity of genetic defects along the same signaling pathway that may lead to combined immune deficiency is paralleled by the heterogeneity of immunological phenotypes that may associate with defects in the same gene, thus creating a need for detailed immunological and molecular investigations in order to dissect the spectrum of combined immune deficiencies in humans.