Mononuciear Cellular Infiltrates in Clinically Involved Skin from Patients with Systemic Sclerosis of Recent Onset Predominantly Consist of Monocytes/Macrophages

Abstract

Systemic sclerosis (SSc) is a generalized autoimmune disorder characterized by immunological abnormalities, microvascular dysfunction, and tissue fibrosis. This study evaluated the inflammatory processes occurring in skin of 7 patients with SSc of recent onset (average disease duration of 10 ± 3 months) to assess the involvement of monocytes/macrophages during the early stages of SSc. All SSc skin biopsies displayed inflammatory microvascular endothelial cell activation and fibrosis. Increased numbers of infiltrating inflammatory leukocytes were present in affected skin of recent onset SSc (p& < 0.01) mainly consisting of CD14-positive monocytes/macrophages (p& < 0.02). CD3 T lymphocytes were only slightly elevated in SSc skin (84 ± 39) compared to normal (51 ± 12), but the differences were statistically not significant. The ratio of CD14/CD3 cells was substantially higher in affected skin of recent onset SSc (4.0 ± 2.0) than in normal skin (1.4 ± 0.5, p& <0.01). Monocytes/ macrophages, therefore, are the predominant infiltrating mononuclear cell in skin lesions of recent-onset SSc. These results strongly suggest that CD 14-positive monocytes/macrophages play an important role during the early stages of SSc pathogenesis.

Is systemic sclerosis an antigen‐driven T cell disease?

“…However, the mechanisms that lead to these changes remain largely unknown. An early skin mononuclear cell infiltrate consisting primarily of T cells and macrophages has been identified (6)(7)(8)(9). The degree of mononuclear cell infiltration in the skin of patients with SSc has been shown to correlate well with both the degree and progression of skin thickening (6).…”

DNA topoisomerase I binding to fibroblasts induces monocyte adhesion and activation in the presence of anti–topoisomerase I autoantibodies from systemic sclerosis patients

“…Monocytic cells are among the first cells to infiltrate the tissues during the onset of SSc (26). The capacity of topo I to recruit SSc anti-topo I to fibroblast cell surfaces prompted us to examine whether this was sufficient to induce subsequent monocyte adhesion.…”

T cells expressing allograft inflammatory factor 1 display increased chemotaxis and induce a profibrotic phenotype in normal fibroblasts in vitro

“…There is strong evidence that chronic tissue inflammation plays a role in this process (7)(8)(9). Prominent mononuclear cell infiltration comprising predominantly macrophages and oligoclonal, activated CD4ϩ T cells is apparent in early SSc lesions (9)(10)(11)(12). Indeed, the presence of several cytokines and growth factors of inflammatory cell origin in the affected tissues in SSc has been described (13,14).…”