Treg‐enriched CD4+ T cells attenuate collagen synthesis in keloid fibroblasts

Abstract

Keloid is an inflammatory and fibrotic disease with an unknown pathogenesis. Regulatory T cells (Tregs) of CD4+ lineage can suppress other effector CD4+ T cells and modulate the immune response. A relative decrease in the number of Tregs may be involved in the pathogenesis of inflammatory and fibrotic diseases. We therefore investigated the number of Tregs in keloids using immunohistochemistry and examined the interaction between Tregs and keloid fibroblasts (KFs) using a coculture system. It was found that the ratio of Tregs/CD4+ T cells was lower compared with that in other common inflammatory skin conditions. In addition, Treg-enriched CD4+ T cells reduced collagen synthesis by KFs. Our findings suggest that a local imbalance of Tregs contributes to the development of keloids and that correction of this imbalance might represent a novel therapeutic approach to keloid fibrosis.

Sulforaphane suppresses cell growth and collagen expression of keloid fibroblasts

“…In contrast, KF112 cells cocultured with PBMC showed a decreased collagen mRNA expression compared with non‐cocultured KF112 cells as previously reported . However, in Western blotting, collagen protein expression in KF112 cells cocultured with PBMC was approximately the same as in non‐cocultured KF112 cells.…”

“…Various coculture systems have been used for the examination of keloid fibroblasts due to the absence of suitable animal models for keloid formation. In this study, we also used PBMC, which infiltrate keloid fibroblasts in keloid tissues, for coculture with KF112 cells . The role of monocytes/macrophages has not yet been fully explored in keloid pathogenesis, but they are thought to be involved in the development of fibrosis by secreting various cytokines and growth factors .…”

A Case of Keloids Complicated by Castleman’s Disease: Interleukin-6 as a Keloid Risk Factor

“…However, it is known that immediately after dermal injury, fibroblasts express IL-6, which then recruits inflammatory cells and stimulates collagen deposition. 12 Moreover, although mature scars bear low levels of IL-6, keloid fibroblasts continue to express IL-6 and its receptors moderately to strongly long after the initial injury. 12 The reasons for this are unclear.…”

“…12 Moreover, although mature scars bear low levels of IL-6, keloid fibroblasts continue to express IL-6 and its receptors moderately to strongly long after the initial injury. 12 The reasons for this are unclear. Further research into how IL-6 shapes keloid development and progression is warranted because this information may aid the development of IL-6 antagonistic drugs that may prevent, ameliorate, or cure keloids.…”

Decorin‐expressing adenovirus decreases collagen synthesis and upregulates MMP expression in keloid fibroblasts and keloid spheroids

“…Keloids and hypertrophic scarring are pathologic fibroproliferative skin disorders that represent abnormal wound healing resulting from excessive collagen production and abnormal collagen assembly, with severely disfiguring results for patients. Various mechanisms have been proposed to explain keloid pathogenesis . However, treatment of keloid scars is extremely difficult because keloids are highly recurrent after surgical excision and often spread beyond the original margin.…”