Regulator of Calcineurin 3 Ameliorates Autoimmune Arthritis by Suppressing Th17 Cell Differentiation

Park, Jin‐Sil; Jeong, Jeong-Hee; Byun, Jae-Kyeong; Lim, Mi Ae; Kim, Min Jung; Kim, Sung‐Min; Choi, Sung Sik; Park, Sung-Hwan; Min, Jun‐Ki; Cho, Mi‐La

doi:10.1016/j.ajpath.2017.05.008

Cited by 14 publications

(16 citation statements)

References 43 publications

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“…The CIA was generated as described previously . On day 7 after the first immunization, mice were injected intravenously with 100 μg of p3XFLAG‐CMV‐10‐CRIF1 or control vector in 2 ml of saline within 5 seconds.…”

Section: Methodsmentioning

confidence: 99%

CR6‐interacting factor 1 controls autoimmune arthritis by regulation of signal transducer and activator of transcription 3 pathway and T helper type 17 cells

et al. 2019

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CR6-interacting factor 1 (CRIF1) is a nuclear protein that interacts with other nuclear factors and androgen receptors, and is implicated in the regulation of cell cycle progression and cell growth. In this study, we examined whether CRIF1 exerts an immunoregulatory effect by modulating the differentiation and function of pathogenic T cells. To this end, the role of CRIF1 in rheumatoid arthritis, a systemic autoimmune disease characterized by hyperplasia of synovial tissue and progressive destruction of articular cartilage structure by pathogenic immune cells [such as T helper type 17 (Th17) cells], was investigated. p3XFLAG-CMV-10-CRIF1 was administered to mice with collagen-induced arthritis 8 days after collagen type II immunization and the disease severity and histologic evaluation, and osteoclastogenesis were assessed. CRIF1 over-expression in mice with collagen-induced arthritis attenuated the clinical and histological signs of inflammatory arthritis. Furthermore, over-expression of CRIF1 in mice with arthritis significantly reduced the number of signal transducer and activator of transcription 3-mediated Th17 cells in the spleen as well as osteoclast differentiation from bone marrow cells. To investigate the impact of loss of CRIF1 in T cells, we generated a conditional CRIF1 gene ablation model using CD4-cre transgenic mice and examined the frequency of Th17 cells and regulatory T cells. Deficiency of CRIF1 in CD4 + cells promoted the production of interleukin-17 and reduced the frequency of regulatory T cells. These results suggest a role for CRIF1 in modulating the activities of Th17 cells and osteoclasts in rheumatoid arthritis.

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Section: Methodsmentioning

confidence: 99%

CR6‐interacting factor 1 controls autoimmune arthritis by regulation of signal transducer and activator of transcription 3 pathway and T helper type 17 cells

et al. 2019

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“…The genes and their corresponding lncRNA-related osteogenesis, cell proliferation, and migration were randomly selected to construct a network diagram. RCAN3, is a calcineurin that affects osteoclasts and participates in osteoclast differentiation 31 . CSF1 is one of the cytokines directly involved in osteoclast differentiation, which could actively regulate the proliferation, differentiation These results revealed that the lncRNAs and genes were differentially expressed in mesenchymal and cartilage tissue, which was consistent with the results of high-throughput sequencing.…”

Section: Discussionmentioning

confidence: 99%

Screening and functional identification of lncRNAs in antler mesenchymal and cartilage tissues using high-throughput sequencing

Chen

Jiang

et al. 2020

Sci Rep

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Long non-coding RNA (lncRNA) is a transcription product of the mammalian genome that regulates the development and growth in the body. The present study aimed to analyze the expression dynamics of lncRNA in sika antler mesenchymal and cartilage tissues by high-throughput sequencing. Bioinformatics was applied to predict differentially expressed lncRNAs and target genes and screen lncRNAs and mRNAs related to osteogenic differentiation, cell proliferation, and migration. Finally, the expression of the lncRNAs and target genes were analyzed by qRT-PCR. The results showed that compared to the cartilage tissue, the transcription levels of lncRNA and mRNA, 1212 lncRNAs and 518 mRNAs, in mesenchymal tissue were altered significantly. Thus, a complex interaction network was constructed, and the lncRNA-mRNA interaction network correlation related to osteogenic differentiation, cell proliferation, and migration was analyzed. Among these, the 26 lncRNAs and potential target genes were verified by qRT-PCR, and the results of qRT-PCR were consistent with high-throughput sequencing results. These data indicated that lncRNA promotes the differentiation of deer antler mesenchymal tissue into cartilage tissue by regulating the related osteogenic factors, cell proliferation, and migration-related genes and accelerating the process of deer antler regeneration and development.

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“…RCAN3 was a favorable prognostic biomarker while PTPRJ was an unfavorable marker in PCPG. RCAN3 not only may be involved in immune response as an endogenous regulator of the calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway, 29 but also plays a vital role in suppression of cancer. 30 PTPRJ, also named CD148, could negatively regulate T-cell activation and play a role in feedback inhibition of T-cell immune responses, 31 which may result in a poor prognosis in PCPG.…”

Section: Dovepressmentioning

confidence: 99%

<p>Comprehensive Analysis of Aberrantly Expressed Competitive Endogenous RNA Network and Identification of Prognostic Biomarkers in Pheochromocytoma and Paraganglioma</p>

Wang

Zhong

et al. 2020

OTT

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Background: Long non-coding RNA (lncRNA) functions as a competitive endogenous RNA (ceRNA) and plays an important role in the biological processes underlying tumorigenesis. However, studies describing the function of lncRNA in pheochromocytoma and paraganglioma (PCPG) remain largely unknown. Our study aims to construct a regulatory ceRNA network and explore prognostic biomarkers for PCPG through a comprehensive analysis. Methods: PCPG data from The Cancer Genome Atlas (TCGA) were utilized to obtain differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs). Kaplan-Meier analysis was used to detect prognostic biomarkers and Cytoscape was utilized to construct a regulatory network of ceRNA. Potential lncRNA-miRNA-mRNA axes were inferred by correlation analysis. GO and KEGG pathways were constructed using "clusterProfiler" and "DOSE" R-packages. Immunohistochemistry (IHC) staining was performed to validate differential protein expression levels of genes in the axes. Finally, the GSE19422 dataset and Pan-Cancer data were applied to validate the expression pattern and survival status of mRNAs, respectively. Results: A total of 334 DElncRNAs, 116 DEmiRNAs, and 3496 DEmRNAs were identified and mainly enriched in hormone secretion, metabolism signaling, metastatic and proliferative pathways. Among these differentially expressed genes, 16 mRNAs, six lncRNAs, and two miRNAs were associated with overall survival of patients with PCPG and sequentially enrolled in the ceRNA network. Two lncRNA-miRNA-mRNA regulatory axes were predicted: AP001486.2/hsa-miR-195-5p/RCAN3 and AP006333.2/hsa-miR-34a-5p/PTPRJ. The GSE19422 dataset and IHC analysis validated that mRNA and protein levels of RCAN3 and PTPRJ were upregulated in PCPG tissues compared with adjacent adrenal gland medulla tissues. Pan-Cancer data showed that the upregulated expression of RCAN3 and PTPRJ was associated with favorable overall survival and disease-free survival. Conclusion: A regulatory lncRNA-miRNA-mRNA ceRNA network was successfully constructed and 24 prognostic biomarkers were identified for PCPG patients. These findings may contribute toward a better understanding of the biological mechanism of tumorigenesis and enable further evaluation of the prognosis of patients with PCPG.

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Regulator of Calcineurin 3 Ameliorates Autoimmune Arthritis by Suppressing Th17 Cell Differentiation

Cited by 14 publications

References 43 publications

CR6‐interacting factor 1 controls autoimmune arthritis by regulation of signal transducer and activator of transcription 3 pathway and T helper type 17 cells

CR6‐interacting factor 1 controls autoimmune arthritis by regulation of signal transducer and activator of transcription 3 pathway and T helper type 17 cells

Screening and functional identification of lncRNAs in antler mesenchymal and cartilage tissues using high-throughput sequencing

<p>Comprehensive Analysis of Aberrantly Expressed Competitive Endogenous RNA Network and Identification of Prognostic Biomarkers in Pheochromocytoma and Paraganglioma</p>

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