Immune cells in keloids: mechanisms and potential treatments

Keloids are a prevalent pathological fibrotic and proliferative disorder characterized by persistent inflammation and immune dysregulation. In recent years, the critical role of immune cells in keloid development and progression has attracted increasing attention.

To summarize the immunoregulatory mechanisms and immune dysfunction involved in keloids and to discuss therapeutic strategies targeting these pathways.

Relevant evidence on immune cell populations and immunoregulatory pathways implicated in keloid pathogenesis was reviewed, with emphasis on regulatory T cells, macrophages, dendritic cells, myeloid-derived suppressor cells, CD8⁺ T cells, and natural killer cells.

Regulatory immune cells, particularly regulatory T lymphocytes (Tregs), exert important effects on keloid formation. Tregs secrete cytokines such as transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10), which suppress inflammation while promoting fibroblast hyperproliferation. M2 macrophages are the predominant macrophage subtype in keloid tissue and contribute to extracellular matrix deposition through the secretion of anti-inflammatory and pro-fibrotic factors. In addition, keloids may exhibit an immune milieu characterized by enrichment of canonical immunoregulatory populations, including regulatory T cells, tolerogenic dendritic cells, and myeloid-derived suppressor cells, together with impaired cytotoxic immune activity involving dysfunctional or exhausted CD8⁺ T cells and natural killer cells. These alterations collectively support an anti-inflammatory yet pro-fibrotic microenvironment that favors keloid persistence and progression.

Immunoregulatory mechanisms and cytotoxic immune dysfunction are central to keloid pathogenesis. Targeting these pathways may provide a basis for the development of novel immunomodulatory strategies to improve keloid outcomes.