Differential roles for the IL-9/IL-9 receptor alpha-chain pathway in systemic and oral antigen-induced anaphylaxis.
Differential roles for the IL-9/IL-9 receptor alpha-chain pathway in systemic and oral antigen-induced anaphylaxis.
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DOI：
10.1016/j.jaci.2009.09.054
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发表时间：
2010-02
影响因子：
14.2
通讯作者：
Hogan, Simon P.
中科院分区：
文献类型：
--
作者：
Osterfeld, Heather;Ahrens, Richard;Strait, Richard;Finkelman, Fred D.;Renauld, Jean-Christophe;Hogan, Simon P.
细胞因子 IL-9 与过敏反应有关，包括食物过敏，但其对肠胃外与口服抗原诱导的过敏反应的贡献仍不清楚。我们试图描述 IL-9/IL-9 受体 a 链 (IL-9R) 途径对肠胃外和口服抗原诱导的过敏反应的作用。野生型、IL-9 缺陷型 (Il92/2) 和 IL-9R 缺陷型 (Il9R2/2) 小鼠遭受被动和主动胃肠外和口服抗原（卵清蛋白 [OVA]）诱导的过敏反应。通过体温下降来衡量全身过敏反应的严重程度；根据分泌性腹泻、肠道肥大细胞增多症和血清鼠肥大细胞蛋白酶 1 水平评估肠道过敏反应。在攻击前施用特定的免疫球蛋白同种型或免疫球蛋白受体阻断抗体，以确定 IgE 和 IgG 途径的作用。对 OVA 致敏的野生型小鼠进行重复口服抗原攻击可诱导全身和肠道受累的过敏反应；两者均依赖于 IgE，并在 Il92/2 和 Il9R2/2 小鼠中减弱。相比之下，OVA 致敏野生型小鼠的肠外 OVA 攻击会诱导全身过敏反应，这与 IL-9/IL-9R 途径无关。引人注目的是，IL-9/IL-9R 通路在胃肠外抗原诱导的 IgG 或 IgE 成分或抗 IgE 和抗 FcgRII/III mAb 诱导的全身过敏反应中没有任何作用。肠外抗原诱导的小鼠全身性过敏反应是由 IgG 和 IgE 依赖性途径介导的，并且两者都可以独立于 IL-9/IL-9R 信号传导而发生。相反，口服抗原诱导的肠道和全身过敏反应严格由 IgE 介导，需要 IL-9/IL-9R 信号传导。这些研究表明 IL-9/IL-9R 通路在全身和口腔抗原诱导的过敏反应中存在差异。
The cytokine IL-9 has been implicated in allergic reactions, including food allergy, but its contribution to parenteral versus oral antigen–induced anaphylaxis remains unclear. We sought to delineate the contribution of the IL-9/IL-9 receptor a-chain (IL-9R) pathway to parenteral and oral antigen–induced anaphylaxis. Wild-type, IL-9–deficient (Il92/2), and IL-9R–deficient (Il9R2/2) mice were subjected to passive and active parenteral and oral antigen (ovalbumin [OVA])-induced anaphylaxis. Severity of systemic anaphylaxis was gauged by decreased body temperature; intestinal anaphylaxis was assessed based on secretory diarrhea, intestinal mastocytosis, and serum murine mast cell protease 1 level. Specific immunoglobulin isotypes or immunoglobulin receptor–blocking antibodies were administered before challenge to define the role of the IgE and IgG pathways. Repeated oral antigen challenge of OVA-sensitized wild-type mice induced anaphylaxis with both systemic and intestinal involvement; both were IgE dependent and attenuated in Il92/2 and Il9R2/2 mice. In contrast, parenteral OVA challenge of OVA-sensitized wild-type mice induced systemic anaphylaxis, which was independent of the IL-9/IL-9R pathway. Strikingly, the IL-9/IL-9R pathway had no role in either the IgG or IgE component of parenteral antigen–induced or anti-IgE and anti-FcgRII/III mAb–induced systemic anaphylaxis. Parenteral antigen–induced murine systemic anaphylaxis is mediated by both IgG- and IgE-dependent pathways, and both can occur independently of IL-9/IL-9R signaling. In contrast, oral antigen–induced intestinal and systemic anaphylaxis is strictly IgE mediated and requires IL-9/IL-9R signaling. These studies indicate differential involvement of the IL-9/IL-9R pathway in systemic and oral antigen–induced anaphylaxis.
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DOI：
10.1165/ajrcmb.19.5.3457
发表时间：
1998-11-01
影响因子：
6.4
作者：
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