AUTHOR=Zhang Jiaxu , Luo Yi , Feng Mingxuan , Xia Qiang 

TITLE=Identification of Liver Immune Microenvironment-Related Hub Genes in Liver of Biliary Atresia

JOURNAL=Frontiers in Pediatrics

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.786422

DOI=10.3389/fped.2021.786422

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> Biliary atresia (BA) is one of the most common and fatal abnormalities of newborns. Increasing evidences indicated that immunology was the critical part of the etiology. This research used a public gene expression database to explore the immune microenvironment of BA liver.</p><p><bold>Methods:</bold> The gene expression profiles GSE46960, GSE159720, and GSE15235, containing BA and normal liver gene expression data, were obtained from the Expression Omnibus Gene. We applied CIBERSORTx to quantify 22 subsets of immune cells in BA liver. The differentially expressed genes (DEGs) and immune cells were used to further explore their relationship with liver fibrosis and the inflammation status of BA.</p><p><bold>Results:</bold> The expression of immune-related genes <italic>CXCL6, CXCL8, CXCL10, CCL20, IL32, TGFB2, SPP1</italic>, and <italic>SLIT2</italic> was significantly different between BA and normal liver, among which <italic>CXCL8</italic> was the hub gene. Six of 22 immune cell proportions were significantly different between BA and normal liver. Specifically, M0 macrophages and resting memory CD4+ T cells were upregulated in BA liver compared with normal liver. Meanwhile, monocytes, resting natural killer (NK) cells, plasma cells, and regulatory T (Treg) cells were downregulated. A further correlation analysis revealed that <italic>SLIT2</italic> and <italic>CXCL6</italic> owned high positive correlation coefficients with fibrosis grade, while the proportion of resting NK cells was negatively correlated. Proportions of resting CD4+ memory T cells were strongly related to the inflammation grade of BA liver.</p><p><bold>Conclusion:</bold> Biliary atresia is a disease strongly correlated with immune response. Our results might provide a clue for further exploration of BA etiology, which may promote a potential prediction model based on immune infiltration features.</p>