Abstract：
The complement active product, C3a, and the receptor C3aR comprise an axis that exerts various biological functions, such as protection against infection. C3a is highly expressed in the inflamed skin and blood from patients with psoriasiform dermatitis. However, the role of the C3a/C3aR axis in psoriasiform dermatitis remains unclear because conflicting results using C3-/- mice have been published. In this study, to elucidate the contribution of commensal microbiota in C3-/- and wild-type (WT) mice were subjected to imiquimod-induced psoriasiform dermatitis under different housing conditions. C3-/- mice showed increased epidermal thickness and keratinocyte proliferation markers in the inflamed ear compared to WT mice upon treatment with IMQ. These inflamed phenotypes were observed in both cohoused and separately housed conditions, and antibiotic treatment did not abolish the aggravation of IMQ-induced psoriasiform dermatitis in C3-/- mice. These results suggested that the difference of commensal microbiota is not important for the C3-involved psoriasiform dermatitis. Keratinocyte hyperproliferation is a major feature of the inflamed skin in patients with psoriasiform dermatitis. In vitro experiments showed that C3a and C3aR agonists inhibited keratinocyte proliferation, which was abolished by introduction of a C3aR antagonist. Collectively, these results suggest that the C3a/C3aR axis plays a critical role in psoriasiform dermatitis development by inhibiting keratinocyte proliferation, regardless of the regulation of the commensal microbiota.
摘要：
补体活性产品，C3a,受体C3aR包含发挥各种生物学功能的轴，例如防止感染。C3a在银屑病样皮炎患者的发炎皮肤和血液中高度表达。然而,C3a/C3aR轴在银屑病样皮炎中的作用尚不清楚,因为使用C3-/-小鼠的结果相互矛盾.在这项研究中,为了阐明在C3-/-和野生型（WT）小鼠中共生微生物群的贡献，在不同的住房条件下对咪喹莫特诱导的银屑病样皮炎进行了治疗。与用IMQ处理的WT小鼠相比,C3-/-小鼠在发炎的耳中显示出增加的表皮厚度和角质形成细胞增殖标志物。这些发炎的表型在共同饲养和单独饲养的条件下都观察到，抗生素治疗并不能消除C3-/-小鼠中IMQ诱导的银屑病样皮炎的加重。这些结果表明，共生微生物群的差异对于C3涉及的银屑病样皮炎并不重要。角质形成细胞过度增殖是银屑病样皮炎患者皮肤发炎的主要特征。体外实验表明C3a和C3aR激动剂抑制角质形成细胞增殖,通过引入C3aR拮抗剂被废除。总的来说，这些结果表明，C3a/C3aR轴通过抑制角质形成细胞增殖在银屑病样皮炎的发展中起关键作用，无论共生微生物群的调节如何。
