src homology 2 domain-containing tyrosine phosphatase SHP-1 controls the development of allergic airway inflammation.
src homology 2 domain-containing tyrosine phosphatase SHP-1 controls the development of allergic airway inflammation.
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DOI：
10.1172/jci15719
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
T. Kamata;M. Yamashita;M. Kimura;Kaoru Murata;M. Inami;C. Shimizu;K. Sugaya;Chrong-Reen Wang;
中科院分区：
文献类型：
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作者：
T. Kamata;M. Yamashita;M. Kimura;Kaoru Murata;M. Inami;C. Shimizu;K. Sugaya;Chrong-Reen Wang;
Th 2细胞在T细胞受体（TCR）识别抗原和IL-4刺激后由初始CD 4 T细胞产生，并且在针对感染性微生物的体液免疫以及过敏性和自身免疫性疾病的发病机制中起关键作用。含有src同源2（SH 2）结构域的酪氨酸磷酸酶SHP-1被认为是各种细胞内信号传导分子（包括TCR和IL-4受体下游的那些分子）的负调节剂。在这里，我们评估的作用，SHP-1在Th 1/Th 2细胞分化和Th 2依赖性过敏性气道炎症的发展，通过使用一个自然的SHP-1突变体，蛾小鼠。CD 4 T细胞似乎在杂合子蛾（me/+）胸腺中正常发育，即使它们表达的SHP-1量减少（约为野生型胸腺水平的三分之一）。me/+初始脾CD 4 T细胞显示出通过IL-4受体介导的信号传导增强的活化，但仅轻微增强TCR介导的信号传导。有趣的是，在me/+小鼠中，Th 2细胞的产生增加，肥大细胞的特异性细胞因子产生增强。在OVA诱导的过敏性气道炎症模型中，me/+小鼠的嗜酸性粒细胞炎症、粘液过度产生和气道高反应性增强。因此，SHP-1可能在过敏反应如过敏性哮喘的发展中起负调节作用。
Th2 cells are generated from naive CD4 T cells upon T cell receptor (TCR) recognition of antigen and IL-4 stimulation and play crucial roles in humoral immunity against infectious microorganisms and the pathogenesis of allergic and autoimmune diseases. A tyrosine phosphatase, SHP-1, that contains src homology 2 (SH2) domains is recognized as a negative regulator for various intracellular signaling molecules, including those downstream of the TCR and the IL-4 receptor. Here we assessed the role of SHP-1 in Th1/Th2 cell differentiation and in the development of Th2-dependent allergic airway inflammation by using a natural SHP-1 mutant, the motheaten mouse. CD4 T cells appear to develop normally in the heterozygous motheaten (me/+) thymus even though they express decreased amounts of SHP-1 (about one-third the level of wild-type thymus). The me/+ naive splenic CD4 T cells showed enhanced activation by IL-4 receptor-mediated signaling but only marginal enhancement of TCR-mediated signaling. Interestingly, the generation of Th2 cells was increased and specific cytokine production of mast cells was enhanced in me/+ mice. In an OVA-induced allergic airway inflammation model, eosinophilic inflammation, mucus hyperproduction, and airway hyperresponsiveness were enhanced in me/+ mice. Thus, SHP-1 may have a role as a negative regulator in the development of allergic responses, such as allergic asthma.