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

Abstract

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 H2O2, 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.

BAP1 Represses Sequential Activation of IRAKs and NF-κB Signaling in Pancreatic Cancer

“…Our study elucidates the negative correlation between BAP1 expression and NF-κB signaling in PDAC patient data and multiple PDAC models. Furthermore, the upregulation of NF-κB due to BAP1 loss has been observed and reported by several researchers 21 , 39 , 40 . However, the specific mechanisms underlying this phenomenon remain unexplained.…”

BAP1 Represses Sequential Activation of IRAKs and NF-κB Signaling in Pancreatic Cancer

“…Our study elucidates the negative correlation between BAP1 expression and NF-κB signaling in PDAC patient data and multiple PDAC models. Furthermore, the upregulation of NF-κB due to BAP1 loss has been observed and reported by several researchers 21 , 39 , 40 . However, the specific mechanisms underlying this phenomenon remain unexplained.…”

TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection

“…The main members of the activator protein-1 (AP-1) family include JUN, JUND, JUNB, and FOS, which orchestrate inflammatory factor-mediated vascular remodeling and cellular proliferation ( Gao et al., 2021 ), and immunomodulatory markers CCL17/TIMD4, associated with M2-like macrophage immunosuppression ( Kuninaka et al., 2022 ). CCL19 facilitates the migration of immune cells ( Takagi-Kimura et al., 2022 ). Tim-4 has been positively correlated with M2-like macrophage-associated inflammatory factors and negatively correlated with fibrosis genes ( Figure 1f ).…”

BAP1 Represses Sequential Activation of IRAKs and NF-κB Signaling in Pancreatic Cancer

“…Our study elucidates the negative correlation between BAP1 expression and NF-κB signaling in PDAC patient data and multiple PDAC models. Furthermore, the upregulation of NF-κB due to BAP1 loss has been observed and reported by several researchers 21 , 39 , 40 . However, the specific mechanisms underlying this phenomenon remain unexplained.…”

TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection

“…The main members of the activator protein-1 (AP-1) family include JUN, JUND, JUNB, and FOS, which orchestrate inflammatory factor-mediated vascular remodeling and cellular proliferation ( Gao et al., 2021 ), and immunomodulatory markers CCL17/TIMD4, associated with M2-like macrophage immunosuppression ( Kuninaka et al., 2022 ). CCL19 facilitates the migration of immune cells ( Takagi-Kimura et al., 2022 ). Tim-4 has been positively correlated with M2-like macrophage-associated inflammatory factors and negatively correlated with fibrosis genes ( Figure 1f ).…”

BAP1 Represses Sequential Activation of IRAKs and NF-κB Signaling in Pancreatic Cancer

“…Our study elucidates the negative correlation between BAP1 expression and NF-κB signaling in PDAC patient data and multiple PDAC models. Furthermore, the upregulation of NF-κB due to BAP1 loss has been observed and reported by several researchers 21 , 39 , 40 . However, the specific mechanisms underlying this phenomenon remain unexplained.…”

TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection

“…The main members of the activator protein-1 (AP-1) family include JUN, JUND, JUNB, and FOS, which orchestrate inflammatory factor-mediated vascular remodeling and cellular proliferation ( Gao et al., 2021 ), and immunomodulatory markers CCL17/TIMD4, associated with M2-like macrophage immunosuppression ( Kuninaka et al., 2022 ). CCL19 facilitates the migration of immune cells ( Takagi-Kimura et al., 2022 ). Tim-4 has been positively correlated with M2-like macrophage-associated inflammatory factors and negatively correlated with fibrosis genes ( Figure 1f ).…”