The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
J Cell Mol Med. 2020 Dec;24(23):14086-14098. doi: 10.1111/jcmm.16020. Epub 2020 Oct 27.
Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory disease with uncertain aetiology. Exosomes are nanosized particles with biological capacities. Here, we aimed to study the effects of T cell-derived exosomes (T-exos) on the pathogenesis of OLP and its mechanism. T-exos were incubated with Jurkat cells for 48 hours, and 26 cytokines in the supernatant were measured by luminex assay. The expression of macrophage inflammatory protein (MIP)-1α/β was detected using immunohistochemistry and ELISA; that of CCR1/3/5 on peripheral T cells was determined by flow cytometry. Transwell assay was performed to investigate the chemotactic effect of MIP-1α/β, and cells in the lower chambers were examinated by flow cytometry. As a result, OLP T-exos elevated the production of MIP-1α/β, which were highly expressed in OLP tissues and plasma. CCR1/5 were markedly expressed on OLP peripheral T cells, and the majority of CCR1/5 T cells were CD8 T cells. Besides, MIP-1α/β promoted the migration of OLP mononuclear cells, while inhibiting CCR1/5 significantly decreased the trafficking of mononuclear cells, especially that of CD8 T cells. Conclusively, OLP T-exos-induced MIP-1α/β may drive the trafficking of CD8 T cells after binding with CCR1/5 in OLP, contributing to the development of OLP.
口腔扁平苔藓(OLP)是一种 T 细胞介导的慢性炎症性疾病,病因不明。外泌体是具有生物功能的纳米级颗粒。在这里,我们旨在研究 T 细胞衍生的外泌体(T-exos)对 OLP 发病机制及其机制的影响。将 T-exos 与 Jurkat 细胞孵育 48 小时,并用 luminex assay 测量上清液中的 26 种细胞因子。用免疫组化和 ELISA 检测巨噬细胞炎性蛋白(MIP)-1α/β的表达;用流式细胞术测定外周 T 细胞上的 CCR1/3/5 的表达。通过 Transwell 测定法研究 MIP-1α/β的趋化作用,并用流式细胞术检查下室中的细胞。结果显示,OLP T-exos 增加了 MIP-1α/β的产生,而 MIP-1α/β在 OLP 组织和血浆中高表达。OLP 外周 T 细胞上 CCR1/5 表达明显,而大多数 CCR1/5 T 细胞为 CD8 T 细胞。此外,MIP-1α/β促进了 OLP 单核细胞的迁移,而显著抑制 CCR1/5 则明显减少了单核细胞的迁移,尤其是 CD8 T 细胞的迁移。总之,OLP T-exos 诱导的 MIP-1α/β可能在与 OLP 中的 CCR1/5 结合后驱动 CD8 T 细胞的迁移,从而促进 OLP 的发展。