In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 108, No. 2 ( 2020-08-01), p. 591-599
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.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
DOI:
10.1002/JLB.3MR0120-203RR
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2026833-6
SSG:
12
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