FcεRI and FcγRIII/CD16 Differentially Regulate Atopic Dermatitis in Mice
FcεRI and FcγRIII/CD16 Differentially Regulate Atopic Dermatitis in Mice
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DOI：
10.4049/jimmunol.0801055
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发表时间：
2009-05-15
影响因子：
4.4
通讯作者：
Dombrowicz, David
中科院分区：
文献类型：
--
作者：
Abboud, Georges;Staumont-Salle, Delphine;Dombrowicz, David
高亲和力IgE受体Fc γ RIII/CD 16和在某些模型中的低亲和力IgG受体Fc γ RIII/CD 16在过敏性疾病中起重要作用。在人类皮肤中，它们存在于募集到发炎真皮中的APC和效应细胞上。FcR γ是在其它FcR中由Fc ε RI和CD 16共享的亚基，并且对于它们的组装和信号转导是必需的。使用再现人类特应性皮炎和特异性FcR缺陷小鼠的一些特征的实验模型，我们在本文中描述了Fc γ RIII/RI和Fc γ RIII/CD 16对病理学的各自贡献。我们证明，特应性皮炎的症状是完全不存在的FcR γ缺陷的动物，但只有部分抑制在Fc γ RIII/CD 16或Fc γ RIII/CD 16缺陷的动物。病理学的缺失或减弱与调节性IL-10和Foxp 3的皮肤表达增加相关。虽然Fc CD 16 RI控制Th 1和Th 2皮肤应答、肥大细胞募集到引流淋巴结和IgE产生，但CD 16仅调节Th 2皮肤应答以及T细胞增殖和IgG I产生。同源FcR的这种同种型特异性调节与引流淋巴结中IL-4和IL-21表达的差异调节相关。因此，Fc β RI和CD 16有助于特应性皮炎，但差异调节与疾病相关的免疫反应。靶向IgE/Fc CD 16和IgG/CD 16相互作用可能是过敏性疾病的有效治疗策略。免疫学杂志，2009，182：6517-6526.
The high-affinity IgE receptor Fc epsilon RI and, in some models, the low-affinity IgG receptor Fc gamma RIII/CD16 play an essential role in allergic diseases. In human skin, they are present on APCs and effector cells recruited into the inflamed dermis. FcR gamma is a subunit shared, among other FcRs, by Fc epsilon RI and CD16 and is essential to their assembly and signal transduction. Using an experimental model reproducing some features of human atopic dermatitis and specific FcR-deficient mice, we have herein delineated the respective contribution of Fc epsilon RI and Fc gamma RIII/CD16 to the pathology. We demonstrate that symptoms of atopic dermatitis are completely absent in FcR gamma-deficient animals but only partially inhibited in either Fc epsilon RI- or Fc gamma RIII/CD16-deficient animals. Absence or attenuation of the pathology is correlated to increased skin expression of regulatory IL-10 and Foxp3. While Fc epsilon RI controls both Th1 and Th2 skin response, mast cell recruitment into draining lymph nodes and IgE production, CD16 regulates only Th2 skin response, as well as T cell proliferation and IgG I production. This isotype-specific regulation by the cognate FcR is associated to a differential regulation of IL-4 and IL-21 expression in the draining lymph nodes. Fc epsilon RI and CD16 thus contribute to atopic dermatitis but differentially regulate immune responses associated with the disease. Targeting both IgE/Fc epsilon RI and IgG/CD16 interactions might represent an efficient therapeutic strategy for allergic diseases. The Journal of Immunology, 2009, 182: 6517-6526.