PU.1, a Shared Transcriptional Regulator of Innate and Adaptive Immune Cell Fates

Singh, Harinder

doi:10.4049/jimmunol.181.3.1595

Cited by 5 publications

(10 citation statements)

References 36 publications

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“…27 Recently, growing evidence has suggested a role for PU.1 in the generation of innate and adaptive immune cells. 28,29 For instance, PU.1 is capable of functioning as a transcriptional regulator in determining the fate of immunocytes such as lymphocyte and dendritic cell lineages. [30][31][32] Moreover, PU.1 critically participates in enhancing the expression of the costimulatory molecules on the cell surface.…”

Section: Discussionmentioning

confidence: 99%

Coordinated regulation of the immunoproteasome subunits by PML/RARα and PU.1 in acute promyelocytic leukemia

Wang

et al. 2013

Oncogene

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Recognition and elimination of malignant cells by cytotoxic T lymphocytes depends on antigenic peptides generated by proteasomes. It has been established that impairment of the immunoproteasome subunits, that is, PSMB8, PSMB9 and PSMB10 (PSMBs), is critical for malignant cells to escape immune recognition. We report here the regulatory mechanism of the repression of PU.1-dependent activation of PSMBs by PML/RARα in the pathogenesis of acute promyelocytic leukemia (APL) and the unidentified function of all-trans retinoic acid (ATRA) as an immunomodulator in the treatment of APL. Chromatin immunoprecipitation and luciferase reporter assays showed that PU.1 directly bound to and coordinately transactivated the promoters of PSMBs, indicating that PSMBs were transcriptional targets of PU.1 and PU.1 regulated their basal expression. Analysis of expression profiling data from a large population of acute myeloid leukemia (AML) patients revealed that the expression levels of PSMBs were significantly lower in APL patients than in non-APL AML patients. Further evidence demonstrated that the decrease in their expression was achieved through PML/RARα-mediated repression of both PU.1-dependent transactivation and PU.1 expression. Moreover, ATRA but not arsenic trioxide induced the expression of PSMBs in APL cells, indicating that ATRA treatment might activate the antigen-processing/presentation machinery. Finally, the above observations were confirmed in primary APL samples. Collectively, our data demonstrate that PML/RARα suppresses PU.1-dependent activation of the immunosubunits, which may facilitate the escape of APL cells from immune surveillance in leukemia development, and ATRA treatment is able to reactivate their expression, which would promote more efficient T-cell-mediated recognition in the treatment.

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Section: Discussionmentioning

confidence: 99%

Coordinated regulation of the immunoproteasome subunits by PML/RARα and PU.1 in acute promyelocytic leukemia

Wang

et al. 2013

Oncogene

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“…Similar findings were observed in patients suffering from critical care insults, trauma, and burns but not a clear timeline for restoration of the immune system to pre-insult was ever defined. The excessive secretion of M-CSF is observed after acute inflammation, and prolonged M-CSF influence is related to MΦ predominance and other immune-aberrancies [ 13 , 30 , 31 ]. Continued M-CSF secretion can be sustained via a positive feedback loop involving either M-CSF and the M-CSF receptor (M-CSFR) or the activation of PU.1 [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…The excessive secretion of M-CSF is observed after acute inflammation, and prolonged M-CSF influence is related to MΦ predominance and other immune-aberrancies [ 13 , 30 , 31 ]. Continued M-CSF secretion can be sustained via a positive feedback loop involving either M-CSF and the M-CSF receptor (M-CSFR) or the activation of PU.1 [ 31 , 32 ]. Consequently, we set up on investigating the activation of PU.1 3 months after surgery as the measure of recovery.…”

Section: Introductionmentioning

confidence: 99%

Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF

et al. 2018

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BackgroundIt has been shown that severe insult to the immune system may trigger prolonged macrophage characteristics associated with excessive release of monocyte colony stimulating factor (M-CSF). However, it is unclear how persistent is the macrophage-like characteristics in circulating monocytes (MO). In this study, 20 patients who underwent non-emergent cardiopulmonary bypass had their monocytes characterized before surgery and 3 months after surgery.MethodsWe assessed the macrophage characteristics of MO using cytokine production, surface marker expression, an ability to stimulate T cells, and methylation of the promoter region of the gene encoding PU.1, a critical component to M-CSF production. MO function as well as activation and differentiation potential were longitudinally assessed.ResultsAt 3 months after cardiopulmonary bypass, monocytes exhibited increased expression of MRP8, transforming growth factor-β/latency-associated peptide, suppressor of cytokine signaling 3 while phagocytic properties were increased. Concomitantly, we observed a decreased expression of CD86, a decreased ability to form regulatory dendritic cells, and a diminished ability to stimulate T cells. These characteristics were accompanied by a persistent increase in the secretion of M-CSF, over-activation of PU.1, and decreased methylation of the PU.1 promoter region. Serum levels of C-reactive protein and anti-cytomegalovirus IgG antibody titers were also elevated in some patients at 3 months after surgery.ConclusionsWe concluded that at 3 months after cardiopulmonary bypass, monocytes continued to express a new macrophage-like milieu that was associated with the persistent activation of the PU.1/M-CSF pathway.

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“…In addition to the VDRE and C/EBP sites, sequence analysis indicated putative PU.1 binding sites in the CAMP promoter (Gombart et al, 2005). PU.1 is a key transcription factor that regulates myeloid and B cell lineage development and has been reported to regulate critical components of the innate immune system (Singh, 2008). PU.1 and C/EBP family members have been reported to co-operate in the regulation of many genes involved in immunity and hematopoiesis including granulocyte macrophage colony stimulating factor receptor and interleukin-1β (IL-1β;Hohaus et al, 1995;Yang, Wara-Aswapati, Chen, Tsukada, & Auron, 2000).…”

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confidence: 99%

PU.1 and epigenetic signals modulate 1,25‐dihydroxyvitamin D₃ and C/EBPα regulation of the human cathelicidin antimicrobial peptide gene in lung epithelial cells

Wei

Dhawan

Baiocchi

et al. 2018

Journal Cellular Physiology

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LL-37, the only known human cathelicidin which is encoded by the human antimicrobial peptide (CAMP) gene, plays a critical role in protection against bacterial infection. We previously demonstrated that cathelicidin is induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in human airway epithelial cells with a resultant increase in bactericidal activity. In this study we identify key factors that cooperate with 1,25(OH)2D3 in the regulation of CAMP. Our results show for the first time that PU.1, the myeloid transcription factor (which has also been identified in lung epithelial cells), cooperates with the vitamin D receptor and C/EBPα to enhance the induction of CAMP in lung epithelial cells. Our findings also indicate that enhancement of 1,25(OH)2D3 regulation of CAMP by histone deacetylase inhibitors involves cooperation between acetylation and chromatin remodeling through BRG1 (a component of the SWI/SNF complex). BRG1 can be an activator or repressor depending on BRG1 associated factors. PRMT5, a methlytransferase which interacts with BRG1, represses 1,25(OH)2D3 induced CAMP in part through dimethylation of H4R3. Our findings identify key mediators involved in the regulation of CAMP gene in lung epithelial cells and suggest new approaches for therapeutic manipulation of gene expression in order to increase the antibacterial capability of the airway.

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PU.1, a Shared Transcriptional Regulator of Innate and Adaptive Immune Cell Fates

Cited by 5 publications

References 36 publications

Coordinated regulation of the immunoproteasome subunits by PML/RARα and PU.1 in acute promyelocytic leukemia

Coordinated regulation of the immunoproteasome subunits by PML/RARα and PU.1 in acute promyelocytic leukemia

Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF

PU.1 and epigenetic signals modulate 1,25‐dihydroxyvitamin D₃ and C/EBPα regulation of the human cathelicidin antimicrobial peptide gene in lung epithelial cells

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PU.1, a Shared Transcriptional Regulator of Innate and Adaptive Immune Cell Fates

Cited by 5 publications

References 36 publications

Coordinated regulation of the immunoproteasome subunits by PML/RARα and PU.1 in acute promyelocytic leukemia

Coordinated regulation of the immunoproteasome subunits by PML/RARα and PU.1 in acute promyelocytic leukemia

Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF

PU.1 and epigenetic signals modulate 1,25‐dihydroxyvitamin D3 and C/EBPα regulation of the human cathelicidin antimicrobial peptide gene in lung epithelial cells

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PU.1 and epigenetic signals modulate 1,25‐dihydroxyvitamin D₃ and C/EBPα regulation of the human cathelicidin antimicrobial peptide gene in lung epithelial cells