Keratinocyte CDw60 expression is modulated by both a Th-1 type cytokine IFN-gamma and Th-2 cytokines IL-4 and IL-13: relevance to psoriasis.
Keratinocyte CDw60 expression is modulated by both a Th-1 type cytokine IFN-gamma and Th-2 cytokines IL-4 and IL-13: relevance to psoriasis.
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角质形成细胞 CDw60 表达受 Th-1 型细胞因子 IFN-γ 和 Th-2 细胞因子 IL-4 和 IL-13 调节：与银屑病相关。
DOI：
10.1046/j.1523-1747.2001.01242.x
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Nickoloff,BJ
中科院分区：
文献类型：
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作者：
Huang,BB;Bonish,BK;Chaturvedi,V;Qin,JZ;Nickoloff,BJ
银屑病是一种慢性皮肤病，免疫细胞浸润，包括活化的T淋巴细胞，产生多种细胞因子，可以影响表皮角质形成细胞的表型。在这些研究中，我们检测了细胞因子干扰素-γ和白细胞介素-13或白细胞介素-4单独和联合对角质形成细胞表面HLA-DR、细胞间粘附分子1和CDw 60以及转录因子STAT 1、STAT 6和BCL-6水平的影响。由于CDw 60是GD 3神经节苷脂的乙酰化形式，可能作为T细胞共刺激分子发挥作用，因此突出了银屑病病变中角质形成细胞对CDw 60表达的调节，以深入了解潜在的重要T细胞-角质形成细胞相互作用。观察到干扰素-γ阻断白细胞介素-4或白细胞介素-13介导的对培养的角质形成细胞上的CDw 60的诱导，但不阻断对转录因子STAT 6的诱导。然而，白细胞介素-13和白细胞介素-4不能阻断干扰素-γ介导的STAT 1或BCL-6的诱导，也不能阻断细胞间粘附分子1和HLA-DR的上调。在银屑病斑块中，CDw 60在急性病变的角质形成细胞上不一致地检测到，但在慢性病变中主要在基底层角质形成细胞上检测到。此外，我们发现，BCL-6水平增加，在银屑病病变;在急性病变BCL-6主要定位于基底层角质形成细胞，而在慢性斑块核BCL-6主要表达的角质形成细胞在基底细胞层。这些研究强调了免疫细胞衍生的细胞因子对角质形成细胞表型的复杂调节，其中涉及白细胞介素-4或白细胞介素-13的CDw 60的诱导被干扰素-γ拮抗。我们认为在银屑病斑块中，角质形成细胞表达CDw 60的存在或不存在可能反映了Th-1型细胞因子如干扰素-γ和Th-2型细胞因子如白细胞介素-4和白细胞介素-13之间的动态相互作用。干扰素-γ诱导转录阻遏物BCL-6的能力也可能有助于皮肤中的总体免疫学事件，包括抑制导致T细胞共刺激神经节苷脂CDw 60表达的合成途径中的中间体。
Psoriasis is a chronic skin disease with an immunocytic infiltrate, including activated T lymphocytes, producing multiple cytokines that can influence the phenotype of epidermal keratinocytes. In these studies we examined the effect of the cytokines interferon-γ and interleukin-13 or interleukin-4 on keratinocytes, alone and in combination, on surface levels of HLA-DR, intercellular adhesion molecule 1, and CDw60, as well as the transcription factors STAT1, STAT6, and BCL-6. As CDw60 is an acetylated form of the GD3ganglioside and may function as a T cell costimulatory molecule, the modulation of CDw60 expression by keratinocytes in psoriatic lesions was highlighted to gain insight into potentially important T cell-keratinocyte interactions. Interferon-γ was observed to block the interleukin-4- or interleukin-13-mediated induction of CDw60 on cultured keratinocytes, but not induction of the transcription factor STAT6. Interleukin-13 and interleukin-4 were unable to block interferon-γ-mediated induction of STAT1 or BCL-6, however, or the upregulation of intercellular adhesion molecule 1 and HLA-DR. In psoriatic plaques, CDw60 was not consistently detected on keratinocytes in acute lesions, but was detected predominantly on basal layer keratinocytes in chronic lesions. In addition we found that BCL-6 levels were increased in psoriatic lesions; in acute lesions BCL-6 was primarily localized in the basal layer keratinocytes, whereas in chronic plaques nuclear BCL-6 was predominantly expressed by keratinocytes in the suprabasal cell layers. These studies highlight the complex modulation of the keratinocyte phenotype by immunocyte-derived cytokines, in which induction of CDw60 involving interleukin-4, or interleukin-13 was antagonized by interferon-γ. We suggest in psoriatic plaques that the presence or absence of CDw60 expression by keratinocytes may reflect the dynamic interplay between Th-1-type cytokines such as interferon-γ and Th-2-type cytokines such as interleukin-4 and interleukin-13. The ability of interferon-γ to induce the transcription repressor BCL-6 may also contribute to the overall immunologic events in skin, including suppression of the intermediates in the synthetic pathway leading to expression of the T cell costimulatory ganglioside CDw60.