The transcription factor Foxp1 regulates the differentiation and function of dendritic cells

Guo, Ziyi; Tao, Yulong; Yin, Shulei; Song, Yingliang; Xin-shi, LU; Li, Xuesong; Fan, Yujuan; Fan, Xiaofang; Xu, Sheng; Yang, Jialin; Yu, Yizhi

doi:10.1016/j.mod.2019.05.001

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…Also, the enriched gene set possesses TFs such as FOXP1, NR5A1, PRDM14, and SOX2. By exploring the function of each of these transcription factors, we found that they include processes associated with the maturation and differentiation of dendritic cells ( 136 , 137 ). To interpret the potential phenotype guided by the inactivation and activation of several TFs in the healthy controls, we identified that most inactive pathways are related to viral infection, immune response, and proinflammatory signaling.…”

Section: Resultsmentioning

confidence: 99%

On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers

et al. 2021

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COVID-19 is a disease with a spectrum of clinical responses ranging from moderate to critical. To study and control its effects, a large number of researchers are focused on two substantial aims. On the one hand, the discovery of diverse biomarkers to classify and potentially anticipate the disease severity of patients. These biomarkers could serve as a medical criterion to prioritize attention to those patients with higher prone to severe responses. On the other hand, understanding how the immune system orchestrates its responses in this spectrum of disease severities is a fundamental issue required to design new and optimized therapeutic strategies. In this work, using single-cell RNAseq of bronchoalveolar lavage fluid of nine patients with COVID-19 and three healthy controls, we contribute to both aspects. First, we presented computational supervised machine-learning models with high accuracy in classifying the disease severity (moderate and severe) in patients with COVID-19 starting from single-cell data from bronchoalveolar lavage fluid. Second, we identified regulatory mechanisms from the heterogeneous cell populations in the lungs microenvironment that correlated with different clinical responses. Given the results, patients with moderate COVID-19 symptoms showed an activation/inactivation profile for their analyzed cells leading to a sequential and innocuous immune response. In comparison, severe patients might be promoting cytotoxic and pro-inflammatory responses in a systemic fashion involving epithelial and immune cells without the possibility to develop viral clearance and immune memory. Consequently, we present an in-depth landscape analysis of how transcriptional factors and pathways from these heterogeneous populations can regulate their expression to promote or restrain an effective immune response directly linked to the patients prognosis.

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Section: Resultsmentioning

confidence: 99%

On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers

et al. 2021

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“…However, in murine bone marrow-derived dendritic cells, silencing Foxp1 inhibits the production and secretion of inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Conversely, overexpression of Foxp1 increases cytokine production [ 43 ]. Knockout of Foxp1 in RPE might repress the cytokines, thereby reducing the stimulation for the production or secretion of VEGF in response to the laser-photocoagulation.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor Foxp1 is essential for the induction of choroidal neovascularization

Yan

et al. 2022

Eye and Vis

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Background The exudative form of age-related macular degeneration (AMD) is characterized by abnormal blood vessel growth, which is stimulated by vascular endothelial growth factor (VEGF) released from retinal pigment epithelium (RPE). The angiogenic behaviors of vascular endothelial cells in vitro depend on forkhead box protein P1 (Foxp1), a transcription repressor widely expressed in human and murine tissues during development. In this study, we aimed to determine whether loss of Foxp1 affects laser-induced choroidal neovascularization (CNV) in mouse. Methods Eye-selective deletion of Foxp1 was obtained by crossing Foxp1flox/flox with Six3-Cre mice. Laser photocoagulation was delivered to six- to eight-week-old mice to induce CNV. The expression of Foxp1 and Cre was determined by immunofluorescence in cryostat sections of the eyes. Fundus fluorescein angiography (FFA), optical coherence tomography (OCT), and B4 isolectin staining were applied to analyze the leakage, bulge height, and area of CNV lesions, respectively. RPE-choroid tissues were isolated for the determination of VEGF and pigment epithelium derived factor (PEDF) by Western blotting. Results Foxp1 was expressed in retinal ganglion cells, RPE, and the choroidal endothelial cells. Laser photocoagulation increased the number of Foxp1+-endothelial cells and induced CNV. Six3-Cre reduced Foxp1 expression in RPE but not the endothelium, leading to a lower level of VEGF in the RPE-choroid. Foxp1 knockout inhibited pathological angiogenesis and vascular leakage of the laser-induced CNV lesions. Conclusions Foxp1 regulates the expression of VEGF in the RPE, and inhibition of Foxp1 could potentially be a novel strategy for the prevention and therapy of neovascularization related to AMD.

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Striking a balance: new perspectives on homeostatic dendritic cell maturation

Bosteels,

Janssens

2024

Nat Rev Immunol

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The transcription factor Foxp1 regulates the differentiation and function of dendritic cells

Cited by 3 publications

References 34 publications

On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers

On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers

Transcription factor Foxp1 is essential for the induction of choroidal neovascularization

Striking a balance: new perspectives on homeostatic dendritic cell maturation

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