HMGB1与促炎TREM-1受体的相互作用产生对HLA阴性肿瘤细胞具有活性的细胞毒性淋巴细胞。

The Interaction of HMGB1 with the Proinflammatory TREM-1 Receptor Generates Cytotoxic Lymphocytes Active against HLA-Negative Tumor Cells.

作者信息

Yurkina Daria M, Romanova Elena A, Feoktistov Alexey V, Soshnikova Natalia V, Tvorogova Anna V, Yashin Denis V, Sashchenko Lidia P

机构信息

Institute of Gene Biology (RAS), Moscow 119334, Russia.

Engelhardt Institute of Molecular Biology (RAS), Moscow 119334, Russia.

出版信息

Int J Mol Sci. 2024 Jan 3;25(1):627. doi: 10.3390/ijms25010627.

DOI:10.3390/ijms25010627

PMID:38203798

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10779375/

Abstract

High mobility group protein (HMGB1) is secreted by myeloid cells and cells of damaged tissues during inflammation, causing inflammatory reactions through various receptors, including TLR and RAGE. TREM-1 is considered to be one of the potential HMGB1 receptors. In this work, we have shown that the HMGB1 protein is able to bind to the TREM-1 receptor at high affinity both in solution and on the cell surface. This binding causes lymphocytes to release cytokines IL-2, IL-1b, IL-6, TNF and Ifny into the medium, which leads to the appearance of cytotoxic lymphocytes in PBMC capable of lysing HLA-negative tumor cells. Expanding the spectra of proinflammatory receptor ligands and understanding the mechanisms of their action is essential for the creation of new immunotherapy pathways.

摘要

高迁移率族蛋白（HMGB1）在炎症过程中由髓样细胞和受损组织的细胞分泌，通过包括TLR和RAGE在内的各种受体引发炎症反应。触发受体表达的髓样细胞分化因子1（TREM-1）被认为是潜在的HMGB1受体之一。在这项研究中，我们已经表明，HMGB1蛋白能够在溶液中和细胞表面以高亲和力与TREM-1受体结合。这种结合导致淋巴细胞将细胞因子白细胞介素-2（IL-2）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子（TNF）和干扰素γ（Ifny）释放到培养基中，这导致外周血单个核细胞（PBMC）中出现能够裂解HLA阴性肿瘤细胞的细胞毒性淋巴细胞。扩展促炎受体配体的谱并了解其作用机制对于创建新的免疫治疗途径至关重要。