JAK3缺陷型重症联合免疫缺陷淋巴细胞中通过IL-2和IL-4的信号传导：JAK3依赖和非依赖途径

Signaling via IL-2 and IL-4 in JAK3-deficient severe combined immunodeficiency lymphocytes: JAK3-dependent and independent pathways.

作者信息

Oakes S A, Candotti F, Johnston J A, Chen Y Q, Ryan J J, Taylor N, Liu X, Hennighausen L, Notarangelo L D, Paul W E, Blaese R M, O'Shea J J

机构信息

Howard Hughes Medical Institute, National Institutes of Health, Research Scholars Program, Bethesda, Maryland 20892, USA.

出版信息

Immunity. 1996 Dec;5(6):605-15. doi: 10.1016/s1074-7613(00)80274-5.

DOI:10.1016/s1074-7613(00)80274-5

PMID:8986719

Abstract

Both IL-2 and IL-4 bind to receptors containing the common gamma chain and JAK3. Although JAK3 is required for proper lymphoid development, the precise roles of this kinase in IL-2 and IL-4 signaling in lymphocytes have not been defined. Here, we have studied IL-2 and IL-4 signaling in B cell lines lacking JAK3. Although IL-2-induced phosphorylation of IL-2R beta, JAK1, and STAT5 all required the presence of JAK3, IL-4-mediated phosphorylation of JAK1, STAT6, and insulin receptor substrates 1 and 2 did not. However, IL-4-induced effects were clearly improved following JAK3 expression. These data indicate that IL-4 signaling occurs in the absence of of JAK3, but is comparatively inefficient. These findings may help in understanding the pathogenesis of the immunodeficiency that occurs with mutations of JAK3 and may suggest a mechanism for the pleiotropic effects of IL-4.

摘要

白细胞介素-2（IL-2）和白细胞介素-4（IL-4）均与含有共同γ链和JAK3的受体结合。尽管JAK3对于正常的淋巴细胞发育是必需的，但该激酶在淋巴细胞中IL-2和IL-4信号传导的确切作用尚未明确。在此，我们研究了缺乏JAK3的B细胞系中的IL-2和IL-4信号传导。尽管IL-2诱导的IL-2Rβ、JAK1和STAT5磷酸化均需要JAK3的存在，但IL-4介导的JAK1、STAT6以及胰岛素受体底物1和2的磷酸化则不需要。然而，JAK3表达后，IL-4诱导的效应明显增强。这些数据表明，IL-4信号传导在没有JAK3的情况下也会发生，但效率相对较低。这些发现可能有助于理解JAK3突变导致的免疫缺陷的发病机制，并可能提示IL-4多效性作用的一种机制。