BAP1 depletion in human B‐lymphoblast cells affects the production of innate immune cytokines and chemokines

Autor: Misato Takagi‐Kimura, Akio Tada, Takashi Kijima, Shuji Kubo, Masaki Ohmuraya, Yoshie Yoshikawa
Rok vydání: 2022
Předmět:
Zdroj: Genes to Cells. 27:731-740
ISSN: 1365-2443
1356-9597
DOI: 10.1111/gtc.12988
Popis: BRCA1 associated protein 1 (BAP1) is a ubiquitin C-terminal hydrolase that deubiquitinates histone H2AK119ub and other proteins and regulates the expression of multiple genes. The knockout of this tumor suppressor gene results in severe thymic atrophy, complete loss of the T cell lineage, and abnormal B cell development in mice. In the current study, we investigated in vitro effects of BAP1 knockout on cytokine and chemokine production using the human B-lymphoblast cell line TSCE5. We confirmed that knockout changed the production of innate immune-associated genes and their receptors. The CCL19, CCR7, CCL2, and CXCR5 genes associated with T and B cell migration were upregulated. Knockout cells producing high levels of CCL19 showed acceleration of actin polymerization, which is essential for cell migration. CD69, PTPRC, and TLR3 genes that activate inflammation were downregulated. The tumor necrosis factor ligand genes TNF, LTA, and TNFSF10 were downregulated by knockout. In knockout cells, TNFα production was strongly downregulated upon the addition of H
Databáze: OpenAIRE
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