Single-cell RNA sequencing reveals distinct immunology profiles in human keloid

Abstract

Keloids, characterized by skin fibrosis and excessive accumulation of extracellular matrix, remain a therapeutic challenge. In this study, we systematically capture the cellular composition of keloids by the single-cell RNA sequencing technique. Our results indicated that there are significant differences in most cell types present between 12 pairs of keloid and adjacent normal tissue. We found that fibroblasts, endothelial cells, mast cells, mural cells, and Schwann cells increased significantly in keloid. The proportion of mesenchymal fibroblast subpopulations in keloids was markedly higher than those in the surrounding normal skin tissue. Furthermore, we found that the immune profiles between two groups varied significantly. The proportion of macrophages in the keloid was significantly elevated compared to the surrounding normal tissue, while cDC2 cells significantly decreased. Hotspot and pseudotime trajectory analysis indicated two modules of macrophage cells (Module2: highly expresses RNASE1, C1QA, CD163, CD14, C1QC, FCGRT, MS4A7; Module10: highly expresses APOC1, CTSB, CTSL, TYROBP), which exhibited the characteristics of tumor-associated macrophages, were upregulated in more-advanced keloid cells. Subsequently, the analysis of cellular communication networks suggested that a macrophage-centered communication regulatory network may exist in keloids and that fibroblasts in keloids may facilitate the transition and proliferation of M2 macrophages, which contributes to further comprehension of the immunological features of keloids. Overall, we delineate the immunology landscape of keloids and present new insights into the mechanisms involved in its formation in this study.

Model for predicting immunotherapy based on M2 macrophage infiltration in TNBC

“…Single-cell sequencing findings have confirmed that MS4A7 is highly expressed in some macrophages (24), and can be used as an immune signature to predict ovarian cancer prognoses (25).…”

“…Single-cell sequencing findings have confirmed that MS4A7 is highly expressed in some macrophages ( 24 ), and can be used as an immune signature to predict ovarian cancer prognoses ( 25 ). SPARC, a CR-mimetic adipokine, induces inflammatory interferon response in macrophages during aging ( 26 ).…”

An updated review of the immunological mechanisms of keloid scars

“…Dysregulation of this process leads to either prolonged inflammation with delayed wound closure or increased scarring. M2 macrophages are disproportionally elevated in keloid lesions ( 69 – 72 , 74 ), in part due to local enrichment of Th2 cytokines. Although not yet verified, M2 dominance has also been linked to macrophage sensitivity to mechanical signals, including skin tension and stiffness ( 42 ).…”

“…On the other hand, reduced expression of potential anti-inflammatory mediators, such as IL-34 and IL-37, has been reported ( 85 , 87 , 95 , 96 ). Single-cell RNA sequencing and spatial transcriptomics ( 72 , 97 – 99 ), as well as epigenetics ( 34 , 100 ) are emerging fields utilized to reveal potential pathophysiological features of keloids. One single-cell RNA sequencing study identified a distinct macrophage-centered communication regulatory network that may favor transition and proliferation of M2 macrophages ( 72 ).…”

“…Single-cell RNA sequencing and spatial transcriptomics ( 72 , 97 – 99 ), as well as epigenetics ( 34 , 100 ) are emerging fields utilized to reveal potential pathophysiological features of keloids. One single-cell RNA sequencing study identified a distinct macrophage-centered communication regulatory network that may favor transition and proliferation of M2 macrophages ( 72 ). In addition to the local characteristics, corresponding abnormalities in the cytokine profile have been identified in the peripheral blood of keloid patients ( 39 ).…”