HBEGF(+) macrophages in rheumatoid arthritis induce fibroblast invasiveness Journal Article


Authors: Kuo, D.; Ding, J.; Cohn, I. S.; Zhang, F.; Wei, K.; Rao, D. A.; Rozo, C.; Sokhi, U. K.; Shanaj, S.; Oliver, D. J.; Echeverria, A. P.; DiCarlo, E. F.; Brenner, M. B.; Bykerk, V. P.; Goodman, S. M.; Raychaudhuri, S.; Rätsch, G.; Ivashkiv, L. B.; Donlin, L. T.
Article Title: HBEGF(+) macrophages in rheumatoid arthritis induce fibroblast invasiveness
Abstract: Macrophages tailor their function according to the signals found in tissue microenvironments, assuming a wide spectrum of phenotypes. A detailed understanding of macrophage phenotypes in human tissues is limited. Using single-cell RNA sequencing, we defined distinct macrophage subsets in the joints of patients with the autoimmune disease rheumatoid arthritis (RA), which affects ~1% of the population. The subset we refer to as HBEGF+ inflammatory macrophages is enriched in RA tissues and is shaped by resident fibroblasts and the cytokine tumor necrosis factor (TNF). These macrophages promoted fibroblast invasiveness in an epidermal growth factor receptor-dependent manner, indicating that intercellular cross-talk in this inflamed setting reshapes both cell types and contributes to fibroblast-mediated joint destruction. In an ex vivo synovial tissue assay, most medications used to treat RA patients targeted HBEGF+ inflammatory macrophages; however, in some cases, medication redirected them into a state that is not expected to resolve inflammation. These data highlight how advances in our understanding of chronically inflamed human tissues and the effects of medications therein can be achieved by studies on local macrophage phenotypes and intercellular interactions. Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Journal Title: Science Translational Medicine
Volume: 11
Issue: 491
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science  
Date Published: 2019-05-08
Start Page: eaau8587
Language: English
DOI: 10.1126/scitranslmed.aau8587
PUBMED: 31068444
PROVIDER: scopus
PMCID: PMC6726376
DOI/URL:
Notes: Article -- Export Date: 3 June 2019 -- Source: Scopus
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MSK Authors
  1. Gunnar Ratsch
    53 Ratsch
  2. David C Kuo
    4 Kuo