Update on macrophages and innate immunity in scleroderma

Area of Science:

• Immunology
• Rheumatology
• Pathogenesis of Scleroderma

Background:

• Scleroderma (systemic sclerosis) is a complex autoimmune disease characterized by inflammation, vascular dysfunction, and fibrosis.
• Innate immune cells, especially macrophages, are increasingly recognized for their significant role in scleroderma pathogenesis.

Purpose of the Study:

• To review recent literature (2014-mid 2015) on the contribution of innate immune cells and signals to scleroderma.
• To elucidate the mechanisms by which macrophages and other innate immune cells influence inflammation, vascular dysfunction, and fibrosis in scleroderma.

Main Methods:

• Literature review of studies published between 2014 and mid-2015.
• Analysis of human and mouse data focusing on innate immune cell involvement in scleroderma.

Main Results:

• Human studies link macrophages to early skin inflammation and lung disease progression in scleroderma.
• Plasmacytoid dendritic cells are implicated in vascular dysfunction.
• Mouse models reveal factors influencing macrophage activation and fibrosis, with emerging evidence of differential myeloid cell effects.
• Toll-like receptor signaling impacts both immune and non-immune cells, influencing inflammation and fibrosis.

Conclusions:

• Multiple innate immune cell types potentially contribute to scleroderma.
• Further investigation into macrophage ontogeny, activation states, and innate signaling pathways within the tissue microenvironment is essential for understanding scleroderma pathogenesis.