Signaling through Fc gamma RIII is required for optimal T helper type (Th)2 responses and Th2-mediated airway inflammation.
Signaling through Fc gamma RIII is required for optimal T helper type (Th)2 responses and Th2-mediated airway inflammation.
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DOI：
10.1084/jem.20061134
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发表时间：
2007-08-06
期刊：
影响因子：
--
通讯作者：
Sperling AI
中科院分区：
文献类型：
--
作者：
Bandukwala HS;Clay BS;Tong J;Mody PD;Cannon JL;Shilling RA;Verbeek JS;Weinstock JV;Solway J;Sperling AI
尽管抑制Fcγ受体已被证明可促进粘膜耐受，但激活Fcγ受体在调节哮喘和过敏的T辅助型（Th）2依赖性炎症反应中的作用尚不清楚。在这里，我们证明了通过激活Fcγ受体和toll样受体4刺激来调节骨髓源性树突状细胞（DCs）的细胞因子产生，并增强其促进Th2反应的能力。低亲和受体FcγRIII的连接是Th2反应增强的特异性需要，因为FcγRIII−/−dc在体内不能增强Th2介导的气道炎症，也不能诱导Th2分化。此外，FcγRIII−/−小鼠Th2细胞因子产生受损，气道炎症减少，而FcγRI−/−小鼠没有发现缺陷。Th2免疫的增强受dc产生的白细胞介素10的调节，但与FcγRIII在增强抗原呈递中的作用不同且独立。因此，我们的研究揭示了FcγRIII信号在调节Th细胞反应中的一种新的特异性作用，并提示除了免疫球蛋白（Ig）E外，抗原特异性IgG也参与了th2介导的疾病如哮喘和过敏的发病机制。
Although inhibitory Fcγ receptors have been demonstrated to promote mucosal tolerance, the role of activating Fcγ receptors in modulating T helper type (Th)2-dependent inflammatory responses characteristic of asthma and allergies remains unclear. Here, we demonstrate that signaling via activating Fcγ receptors in conjunction with Toll-like receptor 4 stimulation modulated cytokine production from bone marrow–derived dendritic cells (DCs) and augmented their ability to promote Th2 responses. Ligation of the low affinity receptor FcγRIII was specifically required for the enhanced Th2 responses, as FcγRIII−/− DCs failed to augment Th2-mediated airway inflammation in vivo or induce Th2 differentiation in vitro. Further, FcγRIII−/− mice had impaired Th2 cytokine production and exhibited reduced airway inflammation, whereas no defect was found in FcγRI−/− mice. The augmentation of Th2 immunity was regulated by interleukin 10 production from the DCs but was distinct and independent of the well-established role of FcγRIII in augmenting antigen presentation. Thus, our studies reveal a novel and specific role for FcγRIII signaling in the regulation of Th cell responses and suggest that in addition to immunoglobulin (Ig)E, antigen-specific IgG also contributes to the pathogenesis of Th2-mediated diseases such as asthma and allergies.
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影响因子：
4.4
作者：
Kane, CM;Cervi, L;Pearce, EJ
通讯作者：
Pearce, EJ
影响因子：
32.4
作者：
Jankovic, D;Kullberg, MC;Sher, A
通讯作者：
Sher, A
影响因子：
32.4
作者：
Barnes, N;Gavin, AL;Hogarth, PM
通讯作者：
Hogarth, PM
影响因子：
32.4
作者：
Ioan-Facsinay, A;de Kimpe, SJ;Verbeek, JS
通讯作者：
Verbeek, JS
DOI：
10.1159/000088881
发表时间：
2006-01-01
期刊：
PARASITES AND ALLERGY
影响因子：
--
作者：
Jankovic, Dragana;Steinfelder, Svenja;Sher, Alan
通讯作者：
Sher, Alan