Macrophages in keloid are potent at promoting the differentiation and function of regulatory T cells

The mechanistic details of keloid formation are still not understood. Given that the immune system is engaged in skin lesion repair, we examined the CD14⁺ macrophages and CD3⁺ T cells in keloid tissues and in the normal skin. Compared to the normal skin, keloid tissues presented significantly elevated infiltration by CD14⁺ macrophages. Moreover, the transcription and protein expression of iNOS, IL-12, IL-10, and TGF-β were significantly higher in keloid macrophages than in normal skin macrophages, in which the expression of M2-associated genes were further elevated compared to M1-associated genes in keloid. We also observed that keloid tissues presented higher infiltration by CD3⁺ T cells, of which the majority was CD4⁺ T cells. Notably, the frequency of Foxp3⁺ regulatory T cells (Tregs) in keloid tissues was significantly higher compared to that in the peripheral blood. Furthermore, macrophages from keloid tissues possessed potent capacity to induce Foxp3 expression in circulating CD3⁺ T cells. Together, this study suggested that macrophages in keloid tissues presented high activation status and were polarized toward the M2 subtype; moreover, these macrophages could promote Treg differentiation by upregulating Foxp3 expression.