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人毛囊中生长抑素的表达及其在免疫豁免中的潜在作用。

Somatostatin expression in human hair follicles and its potential role in immune privilege.

机构信息

Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.

出版信息

J Invest Dermatol. 2013 Jul;133(7):1722-30. doi: 10.1038/jid.2013.53. Epub 2013 Jan 31.

Abstract

Immune privilege (IP) is believed to exist in the anagen hair follicle (HF). Studies have shown that downregulation of major histocompatibility complex Class I occurs and immunosuppressive factors are expressed in the HF bulb and bulge. However, demonstration and quantification of functional IP in HF cells are required. We examined the middle (sheath) and lower (bulb) portions of the human HF using quantitative real-time RT-PCR (qPCR), immunohistology, ELISA, in vitro coculture with peripheral blood mononuclear cells (PBMCs), and flow cytometry. We found that HF cells, relative to non-follicular epidermal cells, failed to promote allogeneic PBMC proliferation and CD4(+) and CD8(+) IFNγ production. By qPCR, we found significant downregulation of Class I and Class II HLA alleles in both the bulb and sheath, and upregulation of multiple immunoregulatory genes. It is noteworthy that somatostatin (SST) was significantly upregulated relative to epidermis. By immunohistochemistry, SST was most strongly expressed in the HF outer root sheath, and, by ELISA, cultured sheath cells secreted SST. PBMCs, cultured with stimulatory allogeneic epidermal cells and SST, secreted significantly less IFNγ than controls. Addition of SST antagonists to PBMCs cocultured with allogeneic HF cells increased IFNγ secretion. The data identify SST as a secretory factor potentially contributing to the HF IP repertoire.

摘要

免疫特权(IP)被认为存在于生长期毛囊(HF)中。研究表明,主要组织相容性复合体 I 类的下调发生在 HF 球部和隆起部,并表达免疫抑制因子。然而,需要证明和量化 HF 细胞中的功能性 IP。我们使用定量实时 RT-PCR(qPCR)、免疫组织化学、ELISA、与外周血单核细胞(PBMC)的体外共培养和流式细胞术检查了人类 HF 的中部(鞘)和下部(球部)。我们发现,与非毛囊表皮细胞相比,HF 细胞不能促进同种异体 PBMC 的增殖和 CD4(+)和 CD8(+) IFNγ的产生。通过 qPCR,我们发现球部和鞘部的 I 类和 II 类 HLA 等位基因均显著下调,多个免疫调节基因上调。值得注意的是,生长抑素(SST)相对于表皮明显上调。通过免疫组织化学,SST 在 HF 外根鞘中表达最强,通过 ELISA 检测,培养的鞘细胞分泌 SST。与有刺激作用的同种异体表皮细胞和 SST 共培养的 PBMC 分泌的 IFNγ明显少于对照组。将 SST 拮抗剂添加到与同种异体 HF 细胞共培养的 PBMC 中会增加 IFNγ 的分泌。数据表明 SST 是一种分泌因子,可能有助于 HF IP 库。

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