Abstract
The non-classical human leukocyte antigen (HLA)-G exerts immune-suppressive properties modulating both NK and T cell responses. While it is physiologically expressed at the maternal-fetal interface and in immune-privileged organs, HLA-G expression is found in tumors and in virus-infected cells. So far, there exists little information about the role of HLA-G and its interplay with immune cells in biopsies, surgical specimen or autopsy tissues of lung, kidney and/or heart muscle from SARS-CoV-2-infected patients compared to control tissues. Heterogeneous, but higher HLA-G protein expression levels were detected in lung alveolar epithelial cells of SARS-CoV-2-infected patients compared to lung epithelial cells from influenza-infected patients, but not in other organs or lung epithelia from non-viral-infected patients, which was not accompanied by high levels of SARS-CoV-2 nucleocapsid antigen and spike protein, but inversely correlated to the HLA-G-specific miRNA expression. High HLA-G expression levels not only in SARS-CoV-2-, but also in influenza-infected lung tissues were associated with a high frequency of tissue-infiltrating immune cells, but low numbers of CD8 + cells and an altered expression of hyperactivation and exhaustion markers in the lung epithelia combined with changes in the spatial distribution of macrophages and T cells. Thus, our data provide evidence for an involvement of HLA-G and HLA-G-specific miRNAs in immune escape and as suitable therapeutic targets for the treatment of SARS-CoV-2 infections.
Keywords: HLA-G; Immune cell infiltration; Immune response; SARS-CoV-2; microRNA.
【저자키워드】 SARS-CoV-2, immune response, HLA-G, Immune cell infiltration, microRNA., 【초록키워드】 Treatment, Macrophage, Tumor, T cells, microRNA, miRNA, lung, surgical, CD8, Autopsy, Spike protein, Antigen, kidney, Immune escape, biopsies, T cell responses, immune cells, distribution, information, expression, SARS-CoV-2 infections, patients, marker, Evidence, Frequency, Immune cell, epithelial cell, therapeutic target, leukocyte, heart muscle, tissue, tissues, expression level, virus-infected cells, specimen, lung tissue, protein expression, organs, miRNA expression, SARS-CoV-2 nucleocapsid, Hyperactivation, while, Cell, lung epithelia, SARS-CoV-2-, changes in, expressed, correlated, lung epithelial cell, accompanied, lung alveolar, modulating, other organ, SARS-CoV-2-infected patient, 【제목키워드】 SARS-COV-2 infection, expression, induction,