M1 polarization of macrophages and their dynamic crosstalk with other cells, such as fibroblasts and lymphocytes, may explain the pathogenesis of hidradenitis suppurativa, providing new therapeutic strategies.
Hidradenitis suppurativa (HS) is a chronic inflammatory dermatological condition involving the perianal, axillary, inguinal, and gluteal areas of the body. The disease pathogenesis is based on the dysregulation of inflammatory responses, predominantly involving macrophages.
In this literature review, published in the International Journal of Dermatology and Venereology, the authors describe macrophage polarization and the crosstalk of macrophages with other cells in HS patients.
Macrophage Polarization
Single-cell RNA sequencing has demonstrated that interferon (IFN)-mediated gene expression stimulates the polarization of macrophages to the M1-like proinflammatory phenotype. This increases phagocytosis, cellular cytotoxicity, and the production of interleukin (IL)-ß and tumor necrosis factor (TNF)-α. In contrast, the number of M2 macrophages decreases in the active inflammatory and non-lesion skin in HS patients.
Crosstalk of Macrophages With Neutrophils and Lymphocytes
The release of neutrophil extracellular trap (NET) by the neutrophils drives the polarization to the M1 phenotype, whereas the release of colony-stimulating factor 1 (CSF-1) induces M2 polarization. Cytokines produced by Th1 and Th2 lymphocytes drive the polarization of macrophages to the M1 and M2 phenotypes, respectively. Macrophages and neutrophils release B-cell activating factor (BAFF) in the HS lesions, which mediates the recruitment of B cells.
Crosstalk of Macrophages With Stromal Cells
Mesenchymal stem cells release chemoattractants to recruit macrophages, increase the count of M2 macrophages at the wound sites, and also promote efferocytosis. Fibroblast-mediated stromal remodeling and tunneling and the epithelization and re-epithelization of these dermal tunnels play an integral role in the chronic inflammatory process and aberrant wound healing in HS patients.
Crosstalk of Macrophages With Keratinocytes and Sebocytes
In HS skin lesions, keratinocytes are responsible for the active recruitment of immune cells to the epidermis, representing crosstalk between keratinocytes and immune cells within the epidermis. Sebocytes also actively participate in the inflammatory processes based on their interaction with the immune cells.
In summary, M1 macrophage polarization, with its infiltration into the body tissues, is an essential part of HS pathogenesis, whereas M2 polarization serves as a potential for treatment interventions.
Source:
Zhang, Q., Feng, Y., Chen, X., Mo, X., Wu, Q., & Qiang, J. (2024). Macrophage Polarization and Crosstalk between Macrophages and Other Cells in Hidradenitis Suppurativa. International Journal of Dermatology and Venereology. https://doi.org/10.1097/jd9.0000000000000382
