The spleen is the site where mast cells are induced in the development of food allergy
The spleen is the site where mast cells are induced in the development of food allergy
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DOI：
10.1093/intimm/dxx005
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发表时间：
2017-01-01
影响因子：
4.4
通讯作者：
Abe, Ryo
中科院分区：
文献类型：
--
作者：
Toyoshima, Shota;Wakamatsu, Ei;Abe, Ryo
据报道，脾脏免疫反应在过敏性疾病的发展中起着关键作用;然而，脾脏的确切作用仍不清楚。在此，我们证明了脾脏在食物过敏（FA）发病机制中的新作用。我们发现肥大细胞（MCs）发展的祖细胞存在于脾抗原特异性T细胞反应过程中在体外。在T（h）2反应介导的FA模型中，在脾脏中也观察到MC显著扩增。脾切除小鼠的过敏性腹泻的发病率大大降低，而过继转移到这些小鼠体内的体外诱导脾MCs恢复过敏症状，这表明脾MCs作为致病细胞在FA的发展。体外生成的MC不仅需要IL-3，还需要IFN-γ，并且用抗IFN-γ抗体治疗FA诱导的小鼠抑制了脾脏中MC的扩增以及腹泻的发展，突出表明脾脏中的IFN-γ协调了FA的发展，随后是局部病变中的T（h）2应答。总的来说，我们认为脾脏在FA发展中的作用是提供一个独特的位点，抗原特异性T细胞诱导致病性MC的发展。
It has been reported that splenic immune responses play pivotal roles in the development of allergic diseases; however, the precise role of the spleen remains unclear. Herein, we demonstrated a novel role of the spleen in the pathogenesis of food allergy (FA). We found that mast cells (MCs) developed from progenitor cells present in spleen during an antigen-specific T-cell response in vitro. In a T(h)2 response-mediated FA model, significant expansion of MCs was also observed in spleen. The incidence of allergic diarrhea was profoundly reduced in splenectomized mice, whereas adoptive transfer of in vitro-induced splenic MCs into these mice restored allergic symptoms, suggesting that the splenic MCs functioned as the pathogenic cells in the development of FA. The in vitro-generated MCs required not only IL-3 but also IFN-gamma, and treatment of FA-induced mice with anti-IFN-gamma antibody suppressed expansion of MCs in spleen as well as diarrhea development, highlighting that IFN-gamma in the spleen orchestrated the development of FA, which was followed by a T(h)2 response in the local lesion. Overall, we propose that the role of the spleen in the development of FA is to provide a unique site where antigen-specific T cells induce development of pathogenic MCs.