4.6 Article

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

Journal

EXPERIMENTAL DERMATOLOGY
Volume 26, Issue 5, Pages 409-415

Publisher

WILEY
DOI: 10.1111/exd.13244

Keywords

B7-H1; CD4(+) T cells; CD8(+) T cells; keratinocytes; oral lichen planus; TLR4

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Funding

  1. National Natural Science Foundation of China [81371147, 81500868, 81170972, 30973311]

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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-B 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.

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