Erdheim-Chester disease: An in vivo human model of Mϕ activation at the crossroad between chronic inflammation and cancer

Giulio Cavalli, Lorenzo Dagna, Riccardo Biavasco, Antonello Villa, Claudio Doglioni, Elisabetta Ferrero, Marina Ferrarini

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)591-599
Number of pages9
JournalJournal of Leukocyte Biology
Issue number2
Publication statusPublished - Aug 1 2020


  • 3D culture
  • BRAF mutation
  • cell metabolism
  • cytokines
  • histiocytosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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