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Involvement of the myeloid cell compartment in fibrogenesis and systemic sclerosis

Nature Reviews Rheumatology volume 15, pages 288–302 (2019)Cite this article

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Abstract

Systemic sclerosis (SSc) is an autoimmune fibrotic disease of unknown aetiology that is characterized by vascular changes in the skin and visceral organs. Autologous haematopoietic stem cell transplantation can improve skin and organ fibrosis in patients with progressive disease and a high risk of organ failure, indicating that cells originating in the bone marrow are important contributors to the pathogenesis of SSc. Animal studies also indicate a pivotal function of myeloid cells in the development of fibrosis leading to changes in the tissue architecture and dysfunction in multiple organs such as the heart, lungs, liver and kidney. In this Review, we summarize current knowledge about the function of myeloid cells in fibrogenesis that occurs in patients with SSc. Targeted therapies currently in clinical studies for SSc might affect myeloid cell-related pathways. Therefore, myeloid cells might be used as cellular biomarkers of disease through the application of high-dimensional techniques such as mass cytometry and single-cell RNA sequencing.

Key points

  • Chronic tissue injury, inflammation and prolonged fibroblast activation lead to fibrosis and organ dysfunction in systemic sclerosis (SSc).

  • Myeloid cells are crucial antigen-presenting cells, regulators of inflammatory responses and producers of cytokines, processes that are implicated in fibrogenesis.

  • Despite comprehensive investigation of myeloid cells, the function of these cells in SSc is not fully understood.

  • High-dimensional analysis of myeloid cells might identify a biomarker of SSc onset and progression.

  • Strategies that target myeloid cell-related pathways might prevent or reverse tissue fibrosis.

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Fig. 1: Crosstalk between innate and adaptive immune responses in fibrogenesis.
Fig. 2: Origin and tissue composition of myeloid cells.
Fig. 3: The fibrosis-promoting functions of monocytes.
Fig. 4: Macrophage-mediated mechanism of fibrosis in the skin and lungs.

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  1. Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich, Zurich, Switzerland

    Gabriela Kania, Michal Rudnik & Oliver Distler

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Kania, G., Rudnik, M. & Distler, O. Involvement of the myeloid cell compartment in fibrogenesis and systemic sclerosis. Nat Rev Rheumatol 15, 288–302 (2019). https://doi.org/10.1038/s41584-019-0212-z

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