TGF-β1-induced transcription factor networks in Langerhans cell development and maintenance

Zhang, Xilin; Gu, Jun; Yu, Fu–Shin X.; Zhou, Li; Mi, Qing‐Sheng

doi:10.1111/all.12871

Cited by 18 publications

(14 citation statements)

References 59 publications

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“…Given that Runx proteins interact with Smad proteins ( Ito and Miyazono, 2003 ), Smad family proteins potentially interact with Runx3/Cbfβ2 complexes to regulate LC differentiation during BMP7-BMPR1A signaling. Although Smad2, Smad3, and Smad4 are not required for LC differentiation in vivo ( Xu et al, 2012 ; Li et al, 2016 ; Zhang et al, 2016 ), it has been reported that BMP7 induces phosphorylation of Smad1/5/8 proteins in vitro ( Yasmin et al, 2013a ). Thus, these Smad1/5/8 proteins might be involved in transmitting signaling from BMPR1A to induce LC differentiation.…”

Section: Discussionmentioning

confidence: 99%

Cbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling

Tenno

Shiroguchi

Muroi

et al. 2017

Journal of Experimental Medicine

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Section: Discussionmentioning

confidence: 99%

Cbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling

Tenno

Shiroguchi

Muroi

et al. 2017

Journal of Experimental Medicine

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“…Chopin and colleagues propose that RUNX3 is vital for mediating LC development, including restraining maturation, which is likely programmed by the TGF-β1-PU.1-RUNX3 transcription axis ( 105 ). Extending Chopin’s work, Zhang and colleagues proposed a collection of TFs and secondary regulators ( 106 ), including RUNX3 ( 107 , 108 ) and STAT5 ( 109 ), as important for LC development and homeostasis. Complementing Chopin’s work on PU.1, counter-regulation between C/EBP and PU.1 might be necessary for LC development, in agreement with the concept of a GRN in which stimulatory and inhibitory interactions between transcriptional partners regulate the network.…”

Section: Grns In Lc Developmentmentioning

confidence: 99%

Langerhans Cells—Programmed by the Epidermis

et al. 2017

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Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels. These cells determine the appropriate adaptive immune response (inflammation or tolerance) by interpreting the microenvironmental context in which they encounter foreign substances. In a normal physiological, “non-dangerous” situation, LCs coordinate a continuous state of immune tolerance, preventing unnecessary and harmful immune activation. Conversely, when they sense a danger signal, for example during infection or when the physical integrity of skin has been compromised as a result of a trauma, they instruct T lymphocytes of the adaptive immune system to mount efficient effector responses. Recent advances investigating the molecular mechanisms underpinning the cross talk between LCs and the epidermal microenvironment reveal its importance for programming LC biology. This review summarizes the novel findings describing LC origin and function through the analysis of the transcriptomic programs and gene regulatory networks (GRNs). Review and meta-analysis of publicly available datasets clearly delineates LCs as distinct from both conventional dendritic cells (DCs) and macrophages, suggesting a primary role for the epidermal microenvironment in programming LC biology. This concept is further supported by the analysis of the effect of epidermal pro-inflammatory signals, regulating key GRNs in human and murine LCs. Applying whole transcriptome analyses and in silico analysis has advanced our understanding of how LCs receive, integrate, and process signals from the steady-state and diseased epidermis. Interestingly, in homeostasis and under immunological stress, the molecular network in LCs remains relatively stable, reflecting a key evolutionary need related to tissue localization. Importantly, to fulfill their key role in orchestrating antiviral adaptive immune responses, LC share specific transcriptomic modules with other DC types able to cross-present antigens to cytotoxic CD8+ T cells, pointing to a possible evolutionary convergence mechanism. With the development of more advanced technologies allowing delineation of the molecular networks at the level of chromatin organization, histone modifications, protein translation, and phosphorylation, future “omics” investigations will bring in-depth understanding of the complex molecular mechanisms underpinning human LC biology.

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“…TGF-β1 could regulate the expression of its downstream genes via transcription factors (TFs) 36 – 38 ; therefore, we searched publicly available TF datasets (PuTmiR, JASPAR, and PROMO) for potential TGF-β signalling-associated TFs that could potentially bind the miR-520h promoter, which identified 15 candidate TFs. Analysis of the mRNA expression of these TFs after stimulation of HO8910 cells with 10 ng/ml TGF-β1 for 48 h, showed that the expression of c-Myb increased the most upon treatment with TGF-β1 (by about 6-fold compared with that in untreated cells, Fig.…”

Section: Resultsmentioning

confidence: 99%

The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression

et al. 2018

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Among the gynaecological cancers, epithelial ovarian cancer (EOC) has the highest lethality because of the high incidence of tumour progression and metastasis. Exploration of the detailed mechanisms underlying EOC metastasis and the identification of crucial targets is important to better estimate the prognosis and improve the treatment of this disease. The present study aimed to identify the role of miR-520h in the prognosis of patients with EOC, and the mechanisms of its involvement in EOC progression. We showed that miR-520h was upregulated in 116 patients with EOC, especially in those with advanced-stage disease, and high miR-520h expression predicted poor outcome. Furthermore, ectopic expression of miR-520h enhanced EOC cell proliferation, migration and invasion, and induced epithelial–mesenchymal transition in vitro and in vivo. miR-520h promoted EOC progression by downregulating Smad7, and subsequently activating the TGF-β signalling pathway. Most importantly, TGF-β1 stimulation increased miR-520h expression in EOC cells by upregulating its transcription factor c-Myb. In conclusion, we described the role of the TGF-β1/c-Myb/miR-520h/Smad7 axis in EOC metastasis, and highlighted the possible use of miR-520h as a prognostic marker for EOC.

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TGF-β1-induced transcription factor networks in Langerhans cell development and maintenance

Cited by 18 publications

References 59 publications

Cbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling

Cbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling

Langerhans Cells—Programmed by the Epidermis

The activation of microRNA-520h–associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression

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