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

  • Misato Takagi‐Kimura
    Department of Genetics, School of Medicine Hyogo Medical University Nishinomiya Japan
  • Akio Tada
    Department of Respiratory Medicine, School of Medicine Hyogo Medical University Nishinomiya Japan
  • Takashi Kijima
    Department of Respiratory Medicine, School of Medicine Hyogo Medical University Nishinomiya Japan
  • Shuji Kubo
    Laboratory of Molecular and Genetic Therapeutics, Institute for Advanced Medical Sciences, School of Medicine Hyogo Medical University Nishinomiya Japan
  • Masaki Ohmuraya
    Department of Genetics, School of Medicine Hyogo Medical University Nishinomiya Japan
  • Yoshie Yoshikawa
    Department of Genetics, School of Medicine Hyogo Medical University Nishinomiya Japan

抄録

<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>BAP1</jats:italic> 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 <jats:italic>CCL19</jats:italic>, <jats:italic>CCR7</jats:italic>, <jats:italic>CCL2</jats:italic>, and <jats:italic>CXCR5</jats:italic> 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. <jats:italic>CD69</jats:italic>, <jats:italic>PTPRC</jats:italic>, and <jats:italic>TLR3</jats:italic> genes that activate inflammation were downregulated. The tumor necrosis factor ligand genes <jats:italic>TNF</jats:italic>, <jats:italic>LTA</jats:italic>, and <jats:italic>TNFSF10</jats:italic> were downregulated by knockout. In knockout cells, TNFα production was strongly downregulated upon the addition of H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>, but NF‐κB in the basal condition and when TNFα was added was augmented, suggesting that these cells could respond to TNFα. These results indicated that BAP1 affects the expression of chemokines and cytokines, T and B cell migration, and activated inflammation associating with innate immunity.</jats:p>

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