Allergin-1 inhibits TLR2-mediated mast cell activation and suppresses dermatitis
Allergin-1 inhibits TLR2-mediated mast cell activation and suppresses dermatitis
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DOI：
10.1093/intimm/dxw046
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发表时间：
2016-12-01
影响因子：
4.4
通讯作者：
Shibuya, Akira
中科院分区：
文献类型：
--
作者：
Tsurusaki, Satoshi;Tahara-Hanaoka, Satoko;Shibuya, Akira
TLR2识别金黄色葡萄球菌的细胞壁成分，金黄色葡萄球菌在90%的特应性湿疹皮肤病变中定植。TLR2信号在皮肤中的调节机制尚不清楚。Allergin-1是一种含有ITIM的抑制性免疫球蛋白样受体，表达于肥大细胞(MC)上，可抑制小鼠的IgE介导的过敏反应。在这里，我们发现Allergin-1在体外抑制TLR2介导的MC的激活和炎性细胞因子的产生。与野生型小鼠相比，Allergin-1基因缺陷小鼠在真皮内注射Pam2CSK4到耳廓后，耳朵肿胀增加，胶原沉积增加，Ly6G(+)中性粒细胞募集增加。利用Mas-treck小鼠，这是一个基于IL4增强子元件的MC缺失系统，我们还证明了MCs上的Allergin-1与Pam2CSK4诱导的耳肿胀有关。这些结果表明，皮肤MC上的Allergin-1可以抑制TLR2诱导的皮炎。
TLR2 recognizes cell wall components of Staphylococcus aureus, which colonizes >90% of atopic eczematous skin lesions. The regulatory mechanisms of TLR2 signaling in the skin remain unclear. Allergin-1, an inhibitory immunoglobulin-like receptor containing an ITIM, is expressed on mast cells (MCs) and inhibits IgE-mediated anaphylaxis in mice. Here, we show that Allergin-1 inhibits TLR2-mediated activation of, and inflammatory cytokine production by, MCs in vitro. Compared with wild-type mice, Allergin-1-deficient mice showed enhanced ear swelling with enhanced collagen deposition and greater Ly6G(+) neutrophil recruitment after intra-dermal injection of Pam2CSK4 into pinnae. Using Mas-TRECK mice, which is an MC deletion system based on il4 enhancer elements, we also demonstrated that Allergin-1 on MCs is responsible for the Pam2CSK4-induced ear swelling. These results suggest that Allergin-1 on skin MCs suppresses TLR2-induced dermatitis.