1. Erdheim-Chester disease: An in vivo human model of Mϕ activation at the crossroad between chronic inflammation and cancer.
- Author
-
Cavalli G, Dagna L, Biavasco R, Villa A, Doglioni C, Ferrero E, and Ferrarini M
- Subjects
- Animals, Cellular Reprogramming, Energy Metabolism, Erdheim-Chester Disease diagnosis, Erdheim-Chester Disease therapy, Histiocytes immunology, Histiocytes metabolism, Histiocytes pathology, Humans, Inflammation etiology, Inflammation metabolism, Inflammation pathology, Macrophage Activation genetics, Mutation, Neoplasms etiology, Neoplasms metabolism, Neoplasms pathology, Oncogenes, Disease Susceptibility, Erdheim-Chester Disease etiology, Erdheim-Chester Disease metabolism, Macrophage Activation immunology, Macrophages immunology, Macrophages metabolism, Signal Transduction
- Abstract
Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by infiltration of multiple tissues by CD68
+ foamy Mϕs (or 'histiocytes'). Clinical manifestations arise from mass-forming lesions or from tissue and systemic inflammation. ECD histiocytes harbor oncogenic mutations along the MAPK-kinase signaling pathway (BRAFV600E in more than half of the patients), and secrete abundant pro-inflammatory cytokines and chemokines. Based on these features, ECD is considered an inflammatory myeloid neoplasm, and is accordingly managed with targeted kinase inhibitors or immunosuppressive and cytokine-blocking agents. Evidence is emerging that maladaptive metabolic changes, particularly up-regulated glycolysis, represent an additional, mutation-driven feature of ECD histiocytes, which sustains deregulated and protracted pro-inflammatory activation and cytokine production. Besides translational relevance to the management of ECD patients and to the development of new therapeutic approaches, recognition of ECD as a natural human model of chronic, maladaptive Mϕ activation instructs the understanding of Mϕ dysfunction in other chronic inflammatory conditions., (©2020 Society for Leukocyte Biology.)- Published
- 2020
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