Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.
Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.
P e e r J P r e P r i n t s | h t t p : / / d x . d o i . o r g / 1 0 . 7 2 8 7 / p e e r j . p r e p r i n t s . PrePrints INTRODUCTIONCC chemokine receptor type 6 (CCR6), a family member of chemokine receptor, was widely expressed in various immune cells (Duhen ﹠ Campbell, 2014; Paradis et al., 2014 ; Wong et al., 2013) The interaction of CCR6 and its distinct ligand CCL20 mediated the migration of immune cells into immune reaction sites (Chen et al., 2011; Kallal et al., 2010). Recent evidence showed that CCR6 also was functional expressed on CD4 + CD25 + regulatory T cells (Tregs) (Rivino et al., 2010). And CCR6 + subset of Tregs, displayed memory/effector phenotype, played an important role in various immune diseases (Kitamura et al., 2010 Lamprecht et al., 2008).Similarly, our recent work further showed that CCR6 + subset of Treg cells were dominantly enriched in tumor mass and closely related to poor prognosis of breast cancer patients (Xu et al., 2010). Notably, the predominant proliferation triggered by DCs was critical for their enrichment and suppressive capacity in tumor mass (Xu et al., 2011). However, the exact regulation mechanism involved in the biological function including proliferation and suppressive capacity of this Tregs subset remains largely unknown, which might be helpful for the Johanson et al., 2014; Danger et al., 2014; Gigli﹠Maizon, 2013). Such as, miR-21 was highly expressed in CD4 + T cells (Sommers et al., 2013).And silencing of miR-21 could alter the proliferation and function of CD4 + T cells (Wang et al., 2014).However, whether CCR6 + Tregs also expressed specific miRNAs pattern and the potential role of these miRNAs in the biological function of these cells remains to be elucidated.To this end, in the present study, the expression pattern of miRNAs in the CCR6 + Tregs was evaluated.Moreover, the mRNA expression profile which might be affected by these miRNAs also was investigated. Our data showed that CCR6 Flow cytometryFlow cytometry was performed on a FACSAria (BD Biosciences) with CellQuest Pro software using directly conjugated mAbs against the following human or murine markers: CD4-PerCP, CD25-allophycocyanin, and CCR6-FITC with corresponding isotype-matched controls (either BD Biosciences or eBioscience Systems).Foxp3 staining was conducted using the Murine Regulatory T cell staining kit (eBioscience) and run according to the manufacturer's protocol. Gene Expression MicroarrayTotal RNA was first converted to cDNA, followed by in vitro transcription to make cRNA. 5 ug of single stranded cDNA was synthesized; end labeled and hybridized, for 16 hours at 45°C, to Mouse Gene 1.0 ST arrays. All washing steps were performed by a GeneChip Fluidics Station 450 and GeneChip were scanned with the Axon GenePix 4000B microarray scanner. Partek was used to determine ANOVA p-values and fold changes for genes. Real time PCRAll reagents, primers, and probes were obtained from Applied Biosystems. A U6 endogenous control was used for normalization. Reverse transcriptase react...
Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4 -/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.
Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4-/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 inhibition using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.
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