Inflammatory Keloid Fibroblasts Promote CCL2-Dependent Monocyte Recruitment and Polarization Toward M2-like Macrophages
Yasmin El MAHI1, Hanane QABALI1, Thomas LIHOREAU2, Brice CHATELAIN3,Céline VIENNET1,4, Francis BONNEFOY1, Gwenaël ROLIN1,4,5
BACKGROUND
Beyond Beyond being a simple fibroproliferative disorder, keloids should be regardedas a chronic inflammatory disease in which inflammation, together with mechanical cues and genetic susceptibility, contributes to the initiation and persistence of tissue fibrosis. This complexity calls for new clinical paradigms to improve keloid management, prevent recurrence, and overcome treatment resistance. At the cellular level, increasing evidence highlights the importance of crosstalk between keloid fibroblasts (KFs) and immune cells, particularly those of the innate immune system, such as mast cells, dendritic cells, and macrophages. Our group previously demonstrated that the accumulation of type 2 macrophages in keloid tissue promotes the acquisition of a more fibrogenic phenotype by keloid fibroblasts (Dirand et al., 2024). In the present study, we aimed to determine how KFs influence monocytes and macrophages during keloid fibrogenesis.
CONCLUSION
As recently reviewed by Guo et al., the CCL2/CCR2 signalling pathway is a major axis involved in the development of fibrotic disorders across multiple organ systems. Here we further contribute to deciphering the role of this pathway in keloid (Liao et al., 2010; Chen et al., 2025). In line with the literature and our previously published data, our work highlights the central role of fibroblast-macrophage crosstalk in keloid fibrosis. Indeed, we suggest that keloid fibroblasts may contribute to sustaining a vicious cycle in which persistent macrophage recruitment and activation continuously amplify tissue fibrosis. In conclusion, CCL2 could be a promising therapeutic target to treat or prevent keloid by disrupting the pathological inflammation/fibrosis loop.
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