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Identification of miRNAs that target Fcγ receptor-mediated phagocytosis during macrophage activation syndrome.
Varsha, Kontham Kulangara; Yang, Xiaoming; Cannon, Alkeiver S; Zhong, Yin; Nagarkatti, Mitzi; Nagarkatti, Prakash.
Afiliación
  • Varsha KK; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC, United States.
  • Yang X; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC, United States.
  • Cannon AS; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC, United States.
  • Zhong Y; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC, United States.
  • Nagarkatti M; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC, United States.
  • Nagarkatti P; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC, United States.
Front Immunol ; 15: 1355315, 2024.
Article en En | MEDLINE | ID: mdl-38558807
ABSTRACT
Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile arthritis, accompanied by cytokine storm and hemophagocytosis. In addition, COVID-19-related hyperinflammation shares clinical features of MAS. Mechanisms that activate macrophages in MAS remain unclear. Here, we identify the role of miRNA in increased phagocytosis and interleukin-12 (IL-12) production by macrophages in a murine model of MAS. MAS significantly increased F4/80+ macrophages and phagocytosis in the mouse liver. Gene expression profile revealed the induction of Fcγ receptor-mediated phagocytosis (FGRP) and IL-12 production in the liver. Phagocytosis pathways such as High-affinity IgE receptor is known as Fc epsilon RI -signaling and pattern recognition receptors involved in the recognition of bacteria and viruses and phagosome formation were also significantly upregulated. In MAS, miR-136-5p and miR-501-3p targeted and caused increased expression of Fcgr3, Fcgr4, and Fcgr1 genes in FGRP pathway and consequent increase in phagocytosis by macrophages, whereas miR-129-1-3p and miR-150-3p targeted and induced Il-12. Transcriptome analysis of patients with MAS revealed the upregulation of FGRP and FCGR gene expression. A target analysis of gene expression data from a patient with MAS discovered that miR-136-5p targets FCGR2A and FCGR3A/3B, the human orthologs of mouse Fcgr3 and Fcgr4, and miR-501-3p targets FCGR1A, the human ortholog of mouse Fcgr1. Together, we demonstrate the novel role of miRNAs during MAS pathogenesis, thereby suggesting miRNA mimic-based therapy to control the hyperactivation of macrophages in patients with MAS as well as use overexpression of FCGR genes as a marker for MAS classification.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Síndrome de Activación Macrofágica Límite: Animals / Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Síndrome de Activación Macrofágica Límite: Animals / Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza