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角质形成细胞上TLR4诱导的B7-H1对口腔扁平苔藓中CD4 T细胞和CD8 T细胞反应起负调节作用。

TLR4-induced B7-H1 on keratinocytes negatively regulates CD4 T cells and CD8 T cells responses in oral lichen planus.

作者信息

Zhang Jing, Tan Ya-Qin, Wei Ming-Hui, Ye Xiao-Jing, Chen Guan-Ying, Lu Rui, Du Ge-Fei, Zhou Gang

机构信息

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

出版信息

Exp Dermatol. 2017 May;26(5):409-415. doi: 10.1111/exd.13244. Epub 2017 Feb 14.

Abstract

Oral lichen planus (OLP) is a T-cell-mediated autoimmune mucocutaneous disease affected by the interactions among the keratinocytes, CD4 T cells and CD8 T cells. B7-H1 induced by Toll-like receptors (TLRs) can suppress T-cell immune reaction, thereby resulting in immune tolerance. However, the role of TLR-mediated B7-H1 on keratinocytes in the immune response of OLP is still unknown. The present study showed that TLR4 could induce time-coursed B7-H1 expression on oral keratinocytes, and blocking NF-κB or PI3K/mTOR pathway downregulated B7-H1 transcriptional expression. Moreover, TLR4-stimulated oral keratinocytes inhibited the proliferation of OLP CD4 T cells and OLP CD8 T cells, and simultaneously prompted their apoptosis. Blockade of keratinocyte-associated B7-H1 restored the declined proliferation of OLP CD4 T cells and OLP CD8 T cells, and prevented their increased apoptosis. Therefore, TLR4-upregulated B7-H1 on keratinocytes could decelerate immune responses of CD4 T cells and CD8 T cells in OLP.

摘要

口腔扁平苔藓(OLP)是一种由T细胞介导的自身免疫性黏膜皮肤疾病,受角质形成细胞、CD4 T细胞和CD8 T细胞之间相互作用的影响。Toll样受体(TLR)诱导的B7-H1可抑制T细胞免疫反应,从而导致免疫耐受。然而,TLR介导的B7-H1在OLP免疫反应中对角质形成细胞的作用仍不清楚。本研究表明,TLR4可诱导口腔角质形成细胞上B7-H1的时间依赖性表达,阻断NF-κB或PI3K/mTOR信号通路可下调B7-H1的转录表达。此外,TLR4刺激的口腔角质形成细胞可抑制OLP CD4 T细胞和OLP CD8 T细胞的增殖,同时促使其凋亡。阻断角质形成细胞相关的B7-H1可恢复OLP CD4 T细胞和OLP CD8 T细胞下降的增殖,并阻止其凋亡增加。因此,角质形成细胞上TLR4上调的B7-H1可减缓OLP中CD4 T细胞和CD8 T细胞的免疫反应。

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