An updated advancement of bifunctional IL-27 in inflammatory autoimmune diseases

Xu, Wang-Dong; Wang, Da-Cheng; Zhao, Ming; Huang, An-Fang

doi:10.3389/fimmu.2024.1366377

Cited by 5 publications

References 220 publications

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Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner

Chawla,

Sharma,

Gau

et al. 2025

MBoC

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Bone is a frequent site for breast cancer metastasis. The vast majority of breast cancer-associated metastasis is osteolytic in nature, and RANKL (receptor activator for nuclear factor κB)-induced differentiation of bone marrow-derived macrophages (BMDMs) to osteoclasts (OCLs) is a key requirement for osteolytic metastatic growth of cancer cells. In this study, we demonstrate that Myocardin-related transcription factor (MRTF) in breast cancer cells plays an important role in paracrine modulation of RANKL-induced osteoclast differentiation. This is partly attributed to MRTF's critical role in maintaining the basal cellular expression of connective tissue growth factor (CTGF), findings that align with a strong positive correlation between CTGF expression and MRTF-A gene signature in the human disease context. Luminex analyses reveal that MRTF depletion in breast cancer cells has a broad impact on OCL-regulatory cell-secreted factors that extend beyond CTGF. Experimental metastasis studies demonstrate that MRTF depletion diminishes OCL abundance and bone colonization breast cancer cells in vivo, suggesting that MRTF inhibition could be an effective strategy to diminish OCL formation and skeletal involvement in breast cancer. In summary, this study highlights a novel tumor-extrinsic function of MRTF relevant to breast cancer metastasis.

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Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner

Chawla,

Sharma,

Gau

et al. 2025

MBoC

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Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner

Chawla,

Sharma,

Gau

et al. 2023

Preprint

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Bone is a frequent site for breast cancer metastasis. Conditioning of local tumor microenvironment through crosstalk between tumor cells and bone resident cells in the metastatic niche is a major driving force for bone colonization of cancer cells. This study demonstrates that Myocardin-related transcription factor (MRTF - a major cofactor for the transcription factor serum-response factor, SRF) activity in breast cancer cells is required for their ability to promote osteoclast differentiation of bone marrow-derived monocytes and colonize in bone. MRTF depletion in breast cancer cells affects a wide range of cell-secreted osteoclast-regulatory factors including connective tissue growth factor (CTGF), a prominent bone metastasis-associated gene that exhibit strong positive association in expression with MRTF activity in human breast cancer. Rescue experiments demonstrate that CTGF is an important paracrine mediator of pro-osteoclastogenic action of MRTF in breast cancer cells. Both SRF-dependent and -independent (SAP-domain directed) functions of MRTF are required for its ability to regulate CTGF expression and osteoclast differentiation. In conclusion, this study uncovers a novel MRTF-directed tumor-extrinsic mechanism of bone colonization of cancer cells and suggest that MRTF inhibition could be a novel strategy to suppress osteoclast activity and skeletal involvement in metastatic breast cancer.

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IL-27 as a novel biomarker for pruritus in nodular prurigo and bullous pemphigoid

Wang,

Zhang,

Teng

et al. 2024

Front. Immunol.

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IntroductionBullous pemphigoid (BP) and prurigo nodularis (PN) are chronic pruritic skin diseases that severely impact patients’ quality of life. Despite the widespread attention these two diseases have garnered within the dermatological field, the specific pathogenesis, particularly the molecular mechanisms underlying the pruritus, remains largely unclear. Limited clinical sequencing studies focusing on BP and PN have hindered the identification of pathological mechanisms and the exploration of effective treatment strategies.MethodsTo address this gap, we collected a total of 23 peripheral blood mononuclear cell samples from BP and PN patients, as well as healthy controls, and performed RNA sequencing analysis. By integrating bioinformatics and machine learning techniques, we aimed to uncover the shared immune regulatory networks and pruritus-related mechanisms between BP and PN.ResultsOur study identified 161 differentially expressed genes shared between BP and PN, which were primarily enriched in immune activation and neural pathways, providing crucial molecular insights into the pruritus-related mechanisms of both diseases. Furthermore, using the machine learning algorithms of support vector machines and random forest, we pinpoint 7 crucial genes shared between the BP and PN databases. Among these, IL-27 emerged as a potential pivotal gene, as its mRNA expression levels strongly correlated with clinical parameters including pruritus scores, immunoglobulin E levels, and eosinophil counts. Validation experiments conducted on clinical samples from an additional 22 participants confirmed the upregulation of IL-27 expression in both BP and PN lesions.DiscussionThis study is the first to unveil the shared inflammatory and immune pathways common to BP and PN, highlighting the critical role of IL-27 in the pathogenesis of these conditions. Our findings not only enhance the understanding of the intricate relationship between BP and PN, but also provide a foundation for the development of novel therapeutic strategies targeting these two dermatological conditions.

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An updated advancement of bifunctional IL-27 in inflammatory autoimmune diseases

Cited by 5 publications

References 220 publications

Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner

Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner

Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner

IL-27 as a novel biomarker for pruritus in nodular prurigo and bullous pemphigoid

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