Profibrotic Activation of Human Macrophages in Systemic Sclerosis.

Arthritis & Rheumatology
Rajan BhandariPatricia A Pioli

Abstract

Genome-wide gene expression studies implicate macrophages as mediators of fibrosis in systemic sclerosis (SSc), but little is known about how these cells contribute to fibrotic activation in SSc. We undertook this study to characterize the activation profile of SSc monocyte-derived macrophages and assessed their interaction with SSc fibroblasts. Plasma and peripheral blood mononuclear cells (PBMCs) were obtained from whole blood from SSc patients (n = 24) and age- and sex-matched healthy controls (n = 12). Monocytes were cultured with autologous or allogeneic plasma to differentiate cells into macrophages. For reciprocal activation studies, macrophages were cocultured with fibroblasts using Transwell plates. The gene expression signature associated with blood-derived human SSc macrophages was enriched in SSc skin in an independent cohort and correlated with skin fibrosis. SSc macrophages expressed surface markers associated with activation and released CCL2, interleukin-6, and transforming growth factor β under basal conditions (n = 8) (P < 0.05). Differentiation of healthy donor monocytes in plasma from SSc patients conferred the immunophenotype of SSc macrophages (n = 13) (P < 0.05). Transwell experiments demonstrated that co...Continue Reading

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Citations

Sep 18, 2020·Current Opinion in Rheumatology·Vincent SobanskiDavid Launay
Sep 23, 2020·Current Rheumatology Reports·Hanlin YinQingran Yan
Oct 16, 2020·Expert Opinion on Emerging Drugs·David RoofehDinesh Khanna
Apr 15, 2021·Advanced Biology·Andrea De PieriKarin Wuertz-Kozak
May 15, 2021·Immunological Reviews·Ronen SchusterBoris Hinz
Sep 2, 2021·Clinical Reviews in Allergy & Immunology·Alain LescoatDinesh Khanna

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