Arru Giannina, Galleri Grazia, Deiana Giovanni A, Zarbo Ignazio R, Sechi Elia, Bo Marco, Cadoni Maria Piera L, Corda Davide G, Frau Claudia, Simula Elena R, Manca Maria Antonietta, Galistu Franca, Solla Paolo, Manetti Roberto, Sechi Gian Pietro, Sechi Leonardo A
Department of Clinical, Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy.
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43b, 07100 Sassari, Italy.
Microorganisms. 2021 Aug 23;9(8):1784. doi: 10.3390/microorganisms9081784.
Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env and HERV-K env were quantified in patients and healthy controls (HCs). HERV-K env glycoprotein was more expressed in B cells and NK cells of ALS patients compared to HCs, whereas HERV-K env transcripts were similar in ALS and HCs. In ALS patients, specific stimulation with HERV-K env peptide showed a higher expression of IL-6 by CD19/B cells. Both peptides, however, were able to induce a great production of IFN-γ by stimulation CD19/B cells, and yielded a higher expression of MIP-1α and a lower expression of MCP-1. HERV-K env peptide induced a great production of TNF-α in CD8/T cells. In conclusion, we observed the ability of HERV-K to modulate the immune system, generating mediators mainly involved in proinflammatory response.
人类内源性逆转录病毒（HERV）-K env-su糖蛋白已在肌萎缩侧索硬化症（ALS）中被记录，其中HERV-K env-su抗体水平与疾病严重程度的临床指标显著相关。在此，我们进一步研究了ALS患者针对源自HERV-K的特定抗原肽的体液免疫和细胞介导免疫反应。对患者和健康对照（HCs）外周血单个核细胞（PBMCs）膜上的HERV-K env糖蛋白表达以及用HERV-K env和HERV-K env刺激后的细胞因子和趋化因子进行了定量分析。与HCs相比，HERV-K env糖蛋白在ALS患者的B细胞和NK细胞中表达更高，而HERV-K env转录本在ALS患者和HCs中相似。在ALS患者中，用HERV-K env肽进行特异性刺激时，CD19/B细胞中IL-6的表达更高。然而，两种肽均能通过刺激CD19/B细胞诱导大量IFN-γ产生，并使MIP-1α表达升高，MCP-1表达降低。HERV-K env肽在CD8/T细胞中诱导大量TNF-α产生。总之，我们观察到HERV-K具有调节免疫系统的能力，可产生主要参与促炎反应的介质。
