Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation

Kim, Kyung Won; Park, Sang Cheol; Cho, Hyung‐Ju; Jang, Haerin; Park, Jaehyun; Shim, Hyo Sup; Kim, Eun Gyul; Kim, Seung Up; Hong, Jung Yeon; Kim, Yoon Hee; Lee, Sanghun; Weiss, Scott T.; Kim, Chang Hoon; Won, Sungho; Sohn, Myung Hyun

doi:10.1016/j.jaci.2020.06.040

Cited by 11 publications

(14 citation statements)

References 35 publications

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“…As a previous report shown, the methylation of MSI2 may contribute to systemic allergic inflammation. [ 33 ] Concordant with our finding, multiple reports have revealed that MSI could activate its downstream Wnt/β‐catenin pathway. [ 24,34 ] Moreover, the crucial role of Wnt/β‐catenin signaling cascade has been reported in obesity.…”

Section: Discussionsupporting

confidence: 91%

Adipocytes‐Derived Exosomal microRNA‐1224 Inhibits M2 Macrophage Polarization in Obesity‐Induced Adipose Tissue Inflammation via MSI2‐Mediated Wnt/β‐Catenin Axis

Zhang

Yao

Teng

et al. 2022

Molecular Nutrition Food Res

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Scope: Phenotypic switch of macrophage polarization in adipose tissue has been associated with obesity-induced adipose tissue inflammation (OATI). Therefore, this study aims to explore the possible mechanism of adipocytes-derived exosomes (ADEs) carrying microRNA-1224 (miR-1224) in M2 macrophage polarization of OATI. Methods and results: miR-1224-knockout (miR-1224-KO) mice for this study, and isolated primary adipocytes from high-fat diet (HFD) or normal diet (SD)-fed mice are developed. ADEs are extracted and cocultured with bone marrow-derived macrophages (BMDMs). The macrophagic crown-like structures (CLS) and M1 and M2 phenotype macrophages in epididymal white adipose tissue (epiWAT) are observed by immunohistochemistry and flow cytometry. The obtained data indicate that miR-1224 is highly expressed in adipose tissues and adipocytes of obese mice. miR-1224 knockout decreases CLS number and increases M2 macrophages polarization in epiWAT. In addition, miR-1224 can be transferred to BMDMs via ADEs, which targeted musashi RNA binding protein 2 (MSI2) expression and inactivated Wnt/𝜷-catenin pathway, inhibiting macrophage M2 polarization and promoting inflammatory factor release. Conclusion: Exosomal miR-1224 derived by adipocytes targets MSI2 and blocks the Wnt/𝜷-catenin pathway, which inhibits macrophage M2 polarization and promotes inflammatory factor release, ultimately promoting OATI.

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Section: Discussionsupporting

confidence: 91%

Adipocytes‐Derived Exosomal microRNA‐1224 Inhibits M2 Macrophage Polarization in Obesity‐Induced Adipose Tissue Inflammation via MSI2‐Mediated Wnt/β‐Catenin Axis

Zhang

Yao

Teng

et al. 2022

Molecular Nutrition Food Res

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“…plays a key role in maintaining the immunosuppressive tumor microenvironment, and the expression of tumor immunosuppressive factors determines the fate and survival status of patients (40). The involvement of Musashi-2 in the regulation of the immune microenvironment, such as modulation of allergic inflammation and interleukin secretion, has also recently been proven (22,41).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of the RNA-binding protein Musashi-2 is associated with immune infiltration and predicts better outcomes in ccRCC patients

Meng²,

You³

et al. 2022

Front. Oncol.

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RNA-binding proteins (RBPs) mainly contribute to abnormalities in posttranscriptional gene regulation. The RBP Musashi-2, an evolutionarily conserved protein, has been characterized as an oncoprotein in various tumors. However, the prognostic value and potential roles of Musashi-2 in clear cell renal cell carcinoma (ccRCC) have not yet been elucidated. In this study, we found that Musashi-2 was mainly expressed in the normal distal tubular cells and collecting duct cells of the kidneys, while its expression was significantly decreased in ccRCC. And higher expression levels of Musashi-2 indicated better overall survival (OS) in ccRCC. Furthermore, immunohistochemistry demonstrated that PD-L1 expression was negatively correlated with Musashi-2 expression, and Musashi-2 was found to be remarkably correlated with multiple immune cells and immune inhibitors, including CD8+ T cells, CD4+ T cells, regulatory T (Treg) cells, PDCD1, CTLA4, Foxp3, and LAG3. Functional enrichment analysis revealed that Musashi-2 might be involved in ccRCC metabolic reprogramming and immune infiltration and further predicted the therapeutic sensitivity of ccRCC. Taken together, Musashi-2 is a prognostic biomarker for ccRCC patients that may provide novel insights into individualized treatment strategies and guide effective immunotherapy.

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“… 28 , 29 Several recent, epigenomic studies in the field of allergic diseases allowed identification of epigenetic signatures of asthma/allergy and are summarized in Table S2 . 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 Additionally, epigenetic mechanisms involved in the development, course, and control of allergic diseases are in detail reviewed elsewhere. 29 , 47 , 58 , 59 , 60 , 61 …”

Section: Basic Omics Strategiesmentioning

confidence: 99%

“… 69 However, methylation profiling microarrays are the most frequently used technology in the allergic diseases research field (Table S2 ). 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 Notably, the recent development of the CRISP/Cas9 technology provides a powerful editing and control toolbox for obtaining a better understanding of epigenetic mechanisms. 47 , 70 For a broad overview of all available approaches in epigenetics, refere to the mentioned references.…”

Section: Basic Omics Strategiesmentioning

confidence: 99%

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Omics technologies in allergy and asthma research: An EAACI position paper

Radzikowska

Baerenfaller

Cornejo-García

et al. 2022

Allergy

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Allergic diseases and asthma are heterogenous chronic inflammatory conditions with several distinct complex endotypes. Both environmental and genetic factors can influence the development and progression of allergy. Complex pathogenetic pathways observed in allergic disorders present a challenge in patient management and successful targeted treatment strategies. The increasing availability of high-throughput omics technologies, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics allows studying biochemical systems and pathophysiological processes underlying allergic responses. Additionally, omics techniques present clinical These different cellular components are tightly interconnected with TA B L E 1 Summary of methods, protocols, and data analysis pipelines most frequently used in omics approaches for allergic diseases research Methods and protocols Data analysis pipeline Mechanisms of allergic diseases Genomics and transcriptomics Microarray 181,182GWAS 183 and RNA microarray bioinformatics 184,185

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Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation

Cited by 11 publications

References 35 publications

Adipocytes‐Derived Exosomal microRNA‐1224 Inhibits M2 Macrophage Polarization in Obesity‐Induced Adipose Tissue Inflammation via MSI2‐Mediated Wnt/β‐Catenin Axis

Adipocytes‐Derived Exosomal microRNA‐1224 Inhibits M2 Macrophage Polarization in Obesity‐Induced Adipose Tissue Inflammation via MSI2‐Mediated Wnt/β‐Catenin Axis

Increased expression of the RNA-binding protein Musashi-2 is associated with immune infiltration and predicts better outcomes in ccRCC patients

Omics technologies in allergy and asthma research: An EAACI position paper

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