Decoy receptors in the regulation of T helper cell type 2 responses.
Decoy receptors in the regulation of T helper cell type 2 responses.
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DOI：
10.1084/jem.20030096
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发表时间：
2003-03-17
期刊：
影响因子：
--
通讯作者：
Fallon PG
中科院分区：
文献类型：
--
作者：
McKenzie AN;Fallon PG
Th2驱动的反应在包括过敏、哮喘和蠕虫感染在内的疾病过程中起重要作用，其特征是产生细胞因子IL-4、IL-5、IL-9和IL-13。这些细胞因子形成了一个复杂的分子和细胞相互作用网络，不仅介导了对蠕虫感染的保护性免疫，而且还诱导了对过敏攻击的不适当炎症反应。考虑到这些分子的临床重要性，已经做出了相当大的努力来试图确定主要的Th2细胞因子在这种疾病过程中的相对贡献。很明显，Th2反应是高度复杂的，可能通过多种途径在多个水平上进行调节，包括对细胞因子和细胞因子受体转录和翻译的时间和空间调节，以启动适当的防御机制，并在感染得到控制后恢复到基础水平。因此，在免疫反应中，某些信号导致特定细胞分泌细胞因子上调，而另一些信号则通过反应细胞导致这些配体的同源受体的表达，导致配体和受体表达重合的细胞激活。然而，由于存在多个具有重叠结合特异性的细胞因子受体，这一模型变得复杂起来。因此，不仅要确定单个细胞因子的作用，而且要确定它们的受体介导的功能。IL-13已被证明是一种极其重要的免疫调节因子，它在疾病病理的发生中的直接作用引发了对能够阻断IL-13在体内的作用的治疗方法的探索。最近的研究使用具有明确的Th2反应的体内模型来研究IL-13的功能生物学。使用IL-13拮抗剂和IL-13缺陷小鼠的互补研究表明，消融IL-13活性深刻地抑制哮喘的病理生理(1-3)，并损害寄生胃肠道蠕虫的排出(4，5)。同样，IL-13在转基因小鼠中过表达
Th2-driven responses are instrumental in disease processes including allergies, asthma, and helminth infection, and are characterized by the production of the cytokines IL-4, IL-5, IL-9, and IL-13. These cytokines form a complex network of molecular and cellular interactions that mediate protective immunity not only to worm infection, but also to induce inappropriate inflammatory responses to allergic challenge. Given the clinical importance of these molecules, considerable effort has gone into attempting to identify the relative contributions of the major Th2 cytokines to such disease processes. It has become apparent that Th2 responses are highly complex and might be regulated at many levels through a multitude of pathways, including temporal and spatial regulation of both cytokine and cytokine receptor transcription and translation, so as to initiate an appropriate defense mechanism as well as return to a basal level once the infection has been controlled. Thus, during an immune response certain signals lead to the upregulation of cytokine secretion by specific cells whereas others lead to the expression of the cognate receptors of these ligands by responding cells, resulting in cellular activation where ligand and receptor expression coincide. However, this model is complicated by the existence of multiple cytokine receptors with overlapping binding specificities. It is important, therefore, not only to determine the roles of the individual cytokines, but also the functions mediated by their receptors.IL-13 has proven to be an extremely important immunoregulator and its direct roles in the generation of disease pathology has triggered the search for therapeutics capable of blocking the actions of IL-13 in vivo. Recent investigations have addressed the functional biology of IL-13 using in vivo models with defined Th2 responses. Complementary studies using IL-13 antagonists and IL-13–deficient mice have demonstrated that ablating IL-13 activity profoundly inhibits the pathophysiology of asthma (1–3) and impairs the expulsion of parasitic gastrointestinal helminths (4, 5). Similarly, overexpression of IL-13 in transgenic mice
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DOI：
10.1165/rcmb.2002-0009oc
发表时间：
2002-10-01
影响因子：
6.4
作者：
Belperio, JA;Dy, M;Keane, MP
通讯作者：
Keane, MP
DOI：
10.1016/s0167-5699(99)01551-0
发表时间：
2000-01-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
Fallon, PG
通讯作者：
Fallon, PG
影响因子：
4.8
作者：
Caput, D;Laurent, P;Ferrara, P
通讯作者：
Ferrara, P
影响因子：
82.9
作者：
Economides, AN;Carpenter, LR;Stahl, N
通讯作者：
Stahl, N
影响因子：
32.4
作者：
Urban, JF;Noben-Trauth, N;Finkelman, FD
通讯作者：
Finkelman, FD