Albanesi C, Scarponi C, Cavani A, Federici M, Nasorri F, Girolomoni G
Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
J Invest Dermatol. 2000 Jul;115(1):81-7. doi: 10.1046/j.1523-1747.2000.00041.x.
Interleukin-17 is a T-cell-derived cytokine, detected in skin affected by allergic contact dermatitis and psoriasis, which regulates keratinocyte expression of adhesion molecules and chemokines. In this study, we have analyzed whether interleukin-17 production segregates with a particular T helper (Th) cell subset, and have examined the capacity of interleukin-17 to modulate the activation of keratinocytes induced by Th1 and Th2 cytokines. A panel of 80 nickel-specific CD4+ T cell clones (36 Th0, 30 Th1, and 14 Th2) was isolated from peripheral blood or lesional skin of allergic contact dermatitis patients. Significant amounts (> 50 pg per ml) of interleukin-17 were released by about 50% of activated Th0, Th1, and Th2 cells. Interleukin-17 alone and in cooperation with interleukin-4, or to a lesser extent with interferon-gamma, decreased the interleukin-1 receptor antagonist to interleukin-1alpha ratio in the supernatants as well as in cell lysates from keratinocytes. In addition, interleukin-17 stimulated the release of growth-regulated oncogene-alpha, granulocyte-macrophage colony stimulating factor, and interleukin-6, with synergistic or additive effects when used together with interferon-gamma or interleukin-4. Interleukin-17 and interleukin-4 also increased stem cell factor release, a function that was inhibited by interferon-gamma. Moreover, interleukin-17 and interleukin-4 enhanced interferon-gamma-induced expression of intercellular adhesion molecule 1, but not CD40, on keratinocytes. The constitutive expression of interleukin-17 and interferon-gamma receptors on keratinocytes was not modulated by interleukin-17, interferon-gamma, or interleukin-4, whereas the interleukin-4 receptor was significantly downregulated by interferon-gamma. As a whole, the results indicate that interleukin-17 can participate relevantly in T-cell-mediated skin immune responses by amplifying both interferon-gamma- and interleukin-4-induced activation of keratinocytes.
白细胞介素-17是一种T细胞衍生的细胞因子，在过敏性接触性皮炎和银屑病累及的皮肤中可检测到，它可调节角质形成细胞黏附分子和趋化因子的表达。在本研究中，我们分析了白细胞介素-17的产生是否与特定的辅助性T（Th）细胞亚群相关，并检测了白细胞介素-17调节由Th1和Th2细胞因子诱导的角质形成细胞活化的能力。从过敏性接触性皮炎患者的外周血或皮损中分离出一组80个镍特异性CD4 + T细胞克隆（36个Th0、30个Th1和14个Th2）。约50%的活化Th0、Th1和Th2细胞释放出大量（>50 pg/ml）的白细胞介素-17。单独的白细胞介素-17以及与白细胞介素-4协同，或在较小程度上与干扰素-γ协同，可降低角质形成细胞培养上清液以及细胞裂解物中白细胞介素-1受体拮抗剂与白细胞介素-1α的比值。此外，白细胞介素-17刺激生长调节致癌基因-α、粒细胞-巨噬细胞集落刺激因子和白细胞介素-6的释放，与干扰素-γ或白细胞介素-4共同使用时具有协同或相加作用。白细胞介素-17和白细胞介素-4还增加干细胞因子的释放，而干扰素-γ可抑制这一功能。此外，白细胞介素-17和白细胞介素-4增强了干扰素-γ诱导的角质形成细胞上细胞间黏附分子1的表达，但未增强CD40的表达。白细胞介素-17、干扰素-γ或白细胞介素-4未调节角质形成细胞上白细胞介素-17和干扰素-γ受体的组成性表达，而干扰素-γ显著下调了白细胞介素-4受体。总体而言，结果表明白细胞介素-17可通过放大干扰素-γ和白细胞介素-4诱导的角质形成细胞活化，显著参与T细胞介导的皮肤免疫反应。
