scholarly journals The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Xiaofei Yu ◽  
Yuhao Wang ◽  
Mi Deng ◽  
Yun Li ◽  
Kelly A Ruhn ◽  
...  

Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differentiates into all known ILC lineages. NFIL3 was required in the common lymphoid progenitor (CLP), and was essential for the differentiation of αLP, a bone marrow cell population that gives rise to all known ILC lineages. Clonal differentiation studies revealed that CXCR6+ cells within the αLP population differentiate into all ILC lineages but not T- and B-cells. We further show that NFIL3 governs ILC development by directly regulating expression of the transcription factor TOX. These findings establish that NFIL3 directs the differentiation of a committed ILC precursor that gives rise to all ILC lineages and provide insight into the defining role of NFIL3 in ILC development.

Agriculture ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 160 ◽  
Author(s):  
Litzy Ayra ◽  
Mario Ramírez ◽  
Luis Íñiguez ◽  
Rosa Rodés ◽  
Eduardo Ortega ◽  
...  

The basic leucine zipper (bZIP) transcription factor family regulates plant developmental processes and response to stresses. The common bean (Phaseolus vulgaris), an important crop legume, possesses a whole set of 78 bZIP (PvbZIP) genes, the majority of these (59%) are most highly expressed in roots and nodules, root-derived new organs formed in the rhizobia N2-fixing symbiosis. Crop production is highly affected by salinity in Cuba and other countries. In this work we characterized the adverse effect of salinity to common bean plants of the Cuban CC-25-9-N cultivar grown in fertilized (full N-content) or symbiotic N-fixation (rhizobia inoculated) conditions. We assessed if PvbZIP TF participate in CC-25-9-N common bean response to salinity. Quantitative reverse-transcriptase-PCR (qRT-PCR) expression analysis showed that 26 out of 46 root/nodule-enhanced PvbZIP, that responded to salt stress in roots and/or nodules from fertilized and N2-fixing CC-25-9-N plants. From public common bean transcriptomic data, we identified 554 genes with an expression pattern similar to that of salt-responsive PvbZIP genes, and propose that the co-expressed genes are likely to be involved in the stress response. Our data provide a foundation for evaluating the individual roles of salt-responsive genes and to explore the PvbZIP-mediated improvement of salt tolerance in common bean.


2013 ◽  
Vol 289 (3) ◽  
pp. 1629-1638 ◽  
Author(s):  
So-ichi Tamai ◽  
Keisuke Imaizumi ◽  
Nobuhiro Kurabayashi ◽  
Minh Dang Nguyen ◽  
Takaya Abe ◽  
...  

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons. Here we show that the basic leucine zipper transcription factor NFIL3 (also called E4BP4) confers neuroprotection in models of ALS. NFIL3 is up-regulated in primary neurons challenged with neurotoxic insults and in a mouse model of ALS. Overexpression of NFIL3 attenuates excitotoxic neuronal damage and protects neurons against neurodegeneration in a cell-based ALS model. Conversely, reduction of NFIL3 exacerbates neuronal demise in adverse conditions. Transgenic neuronal expression of NFIL3 in ALS mice delays disease onset and attenuates motor axon and neuron degeneration. These results suggest that NFIL3 plays a neuroprotective role in neurons and constitutes a potential therapeutic target for neurodegeneration.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kulisara Marupanthorn ◽  
Chairat Tantrawatpan ◽  
Pakpoom Kheolamai ◽  
Duangrat Tantikanlayaporn ◽  
Sirikul Manochantr

AbstractMesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs derived from chorion or placenta is not very efficient. Bone morphogenetic protein-2 (BMP-2) plays an important role in bone development. Its effect on osteogenic augmentation has been addressed in several studies. Recent studies have also shown a relationship between miRNAs and osteogenesis. We hypothesized that miRNAs targeted to Runt-related transcription factor 2 (Runx-2), a major transcription factor of osteogenesis, are responsible for regulating the differentiation of MSCs into osteoblasts. This study examines the effect of BMP-2 on the osteogenic differentiation of MSCs isolated from chorion and placenta in comparison to bone marrow-derived MSCs and investigates the role of miRNAs in the osteogenic differentiation of MSCs from these sources. MSCs were isolated from human bone marrow, chorion and placenta. The osteogenic differentiation potential after BMP-2 treatment was examined using ALP staining, ALP activity assay, and osteogenic gene expression. Candidate miRNAs were selected and their expression levels during osteoblastic differentiation were examined using real-time RT-PCR. The role of these miRNAs in osteogenesis was investigated by transfection with specific miRNA inhibitors. The level of osteogenic differentiation was monitored after anti-miRNA treatment. MSCs isolated from chorion and placenta exhibited self-renewal capacity and multi-lineage differentiation potential similar to MSCs isolated from bone marrow. BMP-2 treated MSCs showed higher ALP levels and osteogenic gene expression compared to untreated MSCs. All investigated miRNAs (miR-31, miR-106a and miR148) were consistently downregulated during the process of osteogenic differentiation. After treatment with miRNA inhibitors, ALP activity and osteogenic gene expression increased over the time of osteogenic differentiation. BMP-2 has a positive effect on osteogenic differentiation of chorion- and placenta-derived MSCs. The inhibition of specific miRNAs enhanced the osteogenic differentiation capacity of various MSCs in culture and this strategy might be used to promote bone regeneration. However, further in vivo experiments are required to assess the validity of this approach.


2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Tao Qiu ◽  
Jiangqiao Zhou ◽  
Tianyu Wang ◽  
Zhongbao Chen ◽  
Xiaoxiong Ma ◽  
...  

AbstractAcute lung injury (ALI) is an acute inflammatory disease. Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing inhibitory receptor that is implicated in various pathological processes. However, the function of LILRB4 in ALI remains largely unknown. The aim of the present study was to explore the role of LILRB4 in ALI. LILRB4 knockout mice (LILRB4 KO) were used to construct a model of ALI. Bone marrow cell transplantation was used to identify the cell source of the LILRB4 deficiency-aggravated inflammatory response in ALI. The effect on ALI was analyzed by pathological and molecular analyses. Our results indicated that LILRB4 KO exacerbated ALI triggered by LPS. Additionally, LILRB4 deficiency can enhance lung inflammation. According to the results of our bone marrow transplant model, LILRB4 regulates the occurrence and development of ALI by bone marrow-derived macrophages (BMDMs) rather than by stromal cells in the lung. The observed inflammation was mainly due to BMDM-induced NF-κB signaling. In conclusion, our study demonstrates that LILRB4 deficiency plays a detrimental role in ALI-associated BMDM activation by prompting the NF-κB signal pathway.


2004 ◽  
Vol 380 (3) ◽  
pp. 695-703 ◽  
Author(s):  
Yongyi BI ◽  
Richard D. PALMITER ◽  
Kristi M. WOOD ◽  
Qiang MA

Phenolic antioxidants, such as tBHQ [2,5-di-(t-butyl)-1,4-hydroquinone], induce Mt1 (metallothionein 1) gene expression and accumulation of MT protein. Induction of Mt1 mRNA does not depend on protein synthesis, and correlates with oxidation–reduction functions of the antioxidants. In the present study, we analysed the biochemical pathway of the induction. Induction depends on the presence of MTF-1 (metal-activated transcription factor 1), a transcription factor that is required for metal-induced transcription of Mt1, but does not require nuclear factor erythroid 2-related factor 2, a tBHQ-activated CNC bZip (cap ‘n’ collar basic leucine zipper) protein, that is responsible for regulating genes encoding phase II drug-metabolizing enzymes. Moreover, tBHQ induces the expression of MRE-βGeo, a reporter gene driven by five metal response elements that constitute an optimal MTF-1 binding site. Reconstitution of Mtf1-null cells with MTF-1 restores induction by both zinc and tBHQ. Unlike activation of phase II genes by tBHQ, induction of Mt1 expression does not occur in the presence of EDTA, when cells are cultured in zinc-depleted medium, or in cells with reduced intracellular ‘free’ zinc due to overexpression of ZnT1, a zinc-efflux transporter, indicating that induction requires zinc. In addition, fluorescence imaging reveals that tBHQ increases cytoplasmic free zinc concentration by mobilizing intracellular zinc pools. These findings establish that phenolic antioxidants activate Mt1 transcription by a zinc-dependent mechanism, which involves MTF-1 binding to metal regulator elements in the Mt1 gene promoter.


Plant Science ◽  
2012 ◽  
Vol 193-194 ◽  
pp. 8-17 ◽  
Author(s):  
Hao Chen ◽  
Wei Chen ◽  
Junli Zhou ◽  
Hang He ◽  
Liangbi Chen ◽  
...  

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