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Macrophages in Systemic Sclerosis: Novel Insights and Therapeutic Implications

  • Scleroderma (J Varga, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Macrophages play key roles in tissue homeostasis and immune surveillance, mobilizing immune activation in response to microbial invasion and promoting wound healing to repair damaged tissue. However, failure to resolve macrophage activation can lead to chronic inflammation and fibrosis, and ultimately to pathology. Activated macrophages have been implicated in the pathogenesis of systemic sclerosis (SSc), although the triggers that induce immune activation in SSc and the signaling pathways that underlie aberrant macrophage activation remain unknown.

Recent Findings

Macrophages are implicated in fibrotic activation in SSc. Targeted therapeutic interventions directed against SSc macrophages may ameliorate inflammation and fibrosis.

Summary

While current studies have begun to elucidate the role of macrophages in disease initiation and progression, further work is needed to address macrophage subset heterogeneity within and among SSc end-target tissues to determine the disparate functions mediated by these subsets and to identify additional targets for therapeutic intervention.

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Abbreviations

SSc:

Systemic sclerosis

ECM:

Extracellular matrix

VEGF:

Vascular endothelial growth factor

pDCs:

Plasmacytoid dendritic cells

MMF:

Mycophenolate mofetil

PFD:

Pirfenidone

IPF:

Idiopathic pulmonary fibrosis

NTD:

Nintedanib

PDGF:

Platelet-derived growth factor

FGF:

Fibroblast growth factor

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Funding

This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases grants R56-AR0639835 and R03-AR068097 (PAP) and by a grant from the Scleroderma Foundation (PAP). DMT received support from the National Institutes of Health p50 Specialized Center Grant, Research Diversity Supplement (3P50AR060780 - 07W1) and the John H. Copenhaver, Jr. and William H. Thomas, MD 1952 Junior Fellowship from Dartmouth Graduate Studies.

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Authors and Affiliations

  1. Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, 705 Remsen, Hanover, NH, 03755, USA

    Diana M. Toledo

  2. Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, 644E Borwell Building, Lebanon, NH, 03756, USA

    Patricia A. Pioli

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  1. Diana M. Toledo
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Correspondence to Patricia A. Pioli.

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Conflict of Interest

Ms. Toledo reports grants from NIH and from Dartmouth Graduate Studies, during the conduct of the study.

Dr. Pioli reports grants from Celdara Medical, LLC, grants from NIH/NIAMS, and grants from Scleroderma Foundation, during the conduct of the study; in addition, Dr. Pioli has a patent Cellular Based Therapies Targeting Disease-Associated Molecular Mediators of Fibrotic, Inflammatory, and Autoimmune Conditions pending.

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Toledo, D.M., Pioli, P.A. Macrophages in Systemic Sclerosis: Novel Insights and Therapeutic Implications. Curr Rheumatol Rep 21, 31 (2019). https://doi.org/10.1007/s11926-019-0831-z

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