IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3 in NC/Nga mice, a model for human atopic dermatitis.
IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3 in NC/Nga mice, a model for human atopic dermatitis.
复制标题
通过增强 NC/Nga 小鼠（人类特应性皮炎模型）中 Janus 激酶 3 的酪氨酸磷酸化，IgE 过度产生。
作者：
M. Matsumoto;C. Ra;K. Kawamoto;H. Sato;A. Itakura;J. Sawada;H. Ushio;H. Suto;K. Mitsuishi;Y. Hikasa;H. Matsuda
特应性皮炎（AD）患者中常见的IgE过度产生可能在AD的发病机制中起重要作用，但其机制尚不清楚。在非无菌环境中饲养的NC/Nga小鼠自发出现AD样皮肤病变，血浆IgE水平升高。我们研究了NC/Nga小鼠中IgE过度产生的机制。来自SPF NC/Nga小鼠的脾T细胞具有与BALB/c小鼠相当的CD 40配体（CD 40 L）表达水平。虽然NC/Nga和BALB/c小鼠的B细胞上的CD 40表达没有差异，但NC/Nga小鼠的B细胞在可溶性CD 40 L和IL-4存在下产生更多的IgE。CD 40 L和/或IL-4的刺激导致B细胞中Janus激酶3（JAK 3）的酪氨酸磷酸化，其在NC/Nga小鼠中的诱导性比在BAL B/c小鼠中更强。在从具有高血清IgE水平的AD患者的PBMC分离的B细胞中，JAK 3在酪氨酸残基处组成性磷酸化，并且其磷酸化通过用CD 40 L和/或IL-4处理而增强，如在具有皮炎和高IgE水平的NC/Nga小鼠的脾B细胞中。因此，这表明，在对CD 40 L和IL-4高度敏感的B细胞中的组成性和增强的JAK 3磷酸化可能归因于NC/Nga小鼠和AD患者中的IgE过度产生。
IgE hyperproduction frequently observed in patients with atopic dermatitis (AD) may greatly contribute to the pathogenesis of AD, but its mechanisms are still unclear. NC/Nga mice raised in nonsterile circumstances spontaneously suffered from AD-like skin lesions with elevation of plasma IgE levels. We investigated mechanisms of the IgE hyperproduction in NC/Nga mice. Splenic T cells from SPF NC/Nga mice had a level of CD40 ligand (CD40L) expression comparable to that of BALB/c mice. Although there was no difference in the expression of CD40 on B cells between NC/Nga and BALB/c mice, B cells of NC/Nga mice produced much more IgE in the presence of soluble CD40L and IL-4. The stimulation with CD40L and/or IL-4 resulted in tyrosine phosphorylation of Janus kinase 3 (JAK3) in B cells, which was more strongly inducible in NC/Nga mice than in BALB/c mice. In B cells isolated from PBMC of AD patients with high serum IgE levels, JAK3 was constitutively phosphorylated at the tyrosine residue, and its phosphorylation was enhanced by the treatment with CD40L and/or IL-4 as was that in splenic B cells of NC/Nga mice with dermatitis and high IgE levels. Thus, it is suggested that constitutive and enhanced JAK3 phosphorylation in B cells highly sensitive to CD40L and IL-4 may be attributable to IgE hyperproduction in NC/Nga mice and patients with AD.
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影响因子：
56.9
作者：
RUSSELL, SM;JOHNSTON, JA;LEONARD, WJ
通讯作者：
LEONARD, WJ
SJA/9 和裸鼠中鼠 IgE 产生的调节。
DOI：
--
发表时间：
1987
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Azuma,M;Hirano,T;Miyajima,H;Watanabe,N;Yagita,H;Enomoto,S;Furusawa,S;Ovary,Z;Kinashi,T;Honjo,T
通讯作者：
Honjo,T
特应性皮炎中抗 CD40 抗体增强 IgE 产生。
DOI：
10.1016/s0091-6749(94)70078-8
发表时间：
1994
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Renz,H;Brodie,C;Bradley,K;Leung,DY;Gelfand,EW
通讯作者：
Gelfand,EW
影响因子：
32.4
作者：
Hanissian, SH;Geha, RS
通讯作者：
Geha, RS
抑制未分离的脾细胞培养物中 IgE 的产生。
影响因子：
4.3
作者：
Maeda-Yoshimoto,K;Hirano,T;Miyajima,H;Nagate,T;Hanada,K;Hirose,S;Okumura,K;Ovary,Z
通讯作者：
Ovary,Z