Transcriptional analysis of murine biliary atresia identifies macrophage heterogeneity and subset-specific macrophage functions.

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Tác giả: Swati Antala, Shang-Yang Chen, Carla M Cuda, Liang Feng, Gaurav Gadhvi, Richard M Green, Kyle D Gromer, William J Janssen, Cara L Mack, Harris Perlman, Colin Shearn, Ronald J Sokol, Sarah A Taylor, Joshua B Wechsler, Deborah R Winter

Ngôn ngữ: eng

Ký hiệu phân loại: 912.01 Philosophy and theory

Thông tin xuất bản: Switzerland : Frontiers in immunology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 57028

 INTRODUCTION: Macrophages play an important role in disease progression of pediatric cholestatic liver disease, particularly biliary atresia (BA)
  however, the restorative versus pathogenic role for precise macrophage subsets remains poorly defined. We aimed to distinguish the transcriptional profiles and roles of defined macrophage subset(s) in murine BA. METHODS: We used multiparameter flow cytometry and RNA-sequencing analysis to profile recruited CD11b RESULTS: Ly6c+ macrophages demonstrated the greatest increase in numbers and percent of total macrophages in murine BA versus saline controls whereas MHCII+ macrophages decreased. Transcriptional changes in murine BA MHCII+ macrophages included reduced expression of the Kupffer cell gene signature, lower expression of genes involved in homeostatic processes, and increased expression of genes involved in inflammatory processes. Ly6c+ macrophages in murine BA showed increased expression for CONCLUSIONS: Our data identify specific pathways upregulated in Ly6c vs MHCII+ macrophage subsets in murine BA. Transcriptional similarities between murine BA and human cholestatic macrophages may enable translation of future mechanistic studies to new macrophage subset-specific therapies.
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