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

Jin, Qi; Gui, Lai; Niu, Feng; Yu, Bing; Lauda, Nicole; Liu, Jianfeng; Mao, Xiaoyan; Chen, Ying

doi:10.1016/j.yexcr.2017.12.011

Cited by 56 publications

(67 citation statements)

References 16 publications

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“…In contrast to previous limited studies, Jin et al (2018) have demonstrated that macrophages were highly active in keloid tissues and were polarized toward the M2 macrophages phenotype. Moreover, these M2 macrophages in keloid tissues could induce regulatory T cells differentiation by upregulating Foxp3 expression (Jin et al, 2018). Furthermore, in keloid tissues, the number of M2 macrophage infiltration might be related to the sensitivity of the glucocorticoid receptor.…”

Section: The Indirect Roles Of Macrophages In the Formation Of Abnormcontrasting

confidence: 97%

Direct and Indirect Roles of Macrophages in Hypertrophic Scar Formation

et al. 2019

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Hypertrophic scars are pathological scars that result from abnormal responses to trauma, and could cause serious functional and cosmetic disability. To date, no optimal treatment method has been established. A variety of cell types are involved in hypertrophic scar formation after wound healing, but the underlying molecular mechanisms and cellular origins of hypertrophic scars are not fully understood. Macrophages are major effector cells in the immune response after tissue injury that orchestrates the process of wound healing. Depending on the local microenvironment, macrophages undergo marked phenotypic and functional changes at different stages during scar pathogenesis. This review intends to summarize the direct and indirect roles of macrophages during hypertrophic scar formation. The in vivo depletion of macrophages or blocking their signaling reduces scar formation in experimental models, thereby establishing macrophages as positive regulatory cells in the skin scar formation. In the future, a significant amount of attention should be given to molecular and cellular mechanisms that cause the phenotypic switch of wound macrophages, which may provide novel therapeutic targets for hypertrophic scars.

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Section: The Indirect Roles Of Macrophages In the Formation Of Abnormcontrasting

confidence: 97%

Direct and Indirect Roles of Macrophages in Hypertrophic Scar Formation

et al. 2019

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“…This may indicate the presence of immune activation in the in ammation stage of keloid development. A study by Jin Q et al identi ed that macrophages in keloid tissues were polarized toward the M2 subtype [8]. In our study, the proportion of M2 in K group was higher than in I group, although the difference was not obvious.…”

Section: Discussioncontrasting

confidence: 61%

“…The distribution of CD1α + Langerhans cells, CD68 + macrophages, and CD20 + B lymphocytes in keloid tissues are also higher than those of normal skin [9]. Moreover, macrophages in keloid tissues are under stress, and can promote Treg cells by regulating Foxp3 differentiation [8]. These suggest that keloid occurrence and development are closely related to the role of immune cell interaction.…”

Section: Introductionmentioning

confidence: 91%

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Characteristics of Tumor Immune Gene and Immune Cell Infiltration during Keloid Formation

Líu

Shan

Wang

et al. 2020

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Background: Keloids are benign fibroproliferative skin tumors that can cause disfigurement and disability. Although current research has sought to examine keloids from the perspectives of genetics, inflammation, immunity, and tumorigenesis, their pathological mechanisms remain unclear. Methods: In this study, we used three datasets of tumor immune gene expression profiling from the normal skin tissue of keloid patients (N group), inflammation tissue of keloid patients (I group), and keloid tissue of keloid patients (K group) to describe the occurrence and characteristics of keloid development. Tumor immune-related genes were analyzed, and the differentially expressed genes (DEGs) between the three groups were compared. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out to determine the main functions of the differentially expressed genes and keloid-related pathways. Results: We identified several genes that may play an important role in keloid development. These genes are CCR1, SELL, CCR7, CD40LG, CD69, CXCL8, ITGAM, ITGAX, CD86, and CXCL9. GO analysis revealed that there were variations in biological processes (BP) between I group and N group, including regulation of lymphocyte activation and T-cell activation. Similar variations were also found between I group and K group, which may play an important role in keloid initiation and formation. Variations in molecular function (MF) were markedly enriched in cytokine receptor binding and receptor ligand activity. Analysis of the KEGG pathway between I group and N group revealed that DEGs were primarily enriched in cytokine−cytokine receptor interaction and viral protein interaction with cytokine and cytokine receptor. We identified a higher proportion of M2 macrophages in N group than in I group, although the difference was not obvious. M1 macrophage production differed significantly between I group and K group. The proportions of CD8+T cells varied significantly between N group and K group. We traced multiple tumor immune-related hub genes from keloid formation and analyzed immune cell subsets in keloid development. Possible molecular mechanisms were described in this study using bioinformatics. Conclusions: These results provide another possibility to elucidate keloid pathogenesis and therapeutic targets in terms of tumor immune gene expression.

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“…Bagabir et al (39) show that the number of CD3 + and CD4 + T lymphocytes underneath the epidermis overlying KLs is significantly higher than in normal skin and scar tissue (121). VDR expressed on CD4 + cells has been shown to have high affinity for VD (122), and T H 17 cells which produce IL-17 have many VDR transcripts (123).…”

Section: Immune System and Vitamin D In Keloid Disordersmentioning

confidence: 99%

The Role of the Renin-Angiotensin System and Vitamin D in Keloid Disorder—A Review

et al. 2019

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Keloid disorder (KD) is a fibroproliferative condition characterized by excessive dermal collagen deposition in response to wounding and/or inflammation of the skin. Despite intensive research, treatment for KD remains empirical and unsatisfactory. Activation of the renin-angiotensin system (RAS) leads to fibrosis in various organs through its direct effect and the resultant hypertension, and activation of the immune system. The observation of an increased incidence of KD in dark-skinned individuals who are predisposed to vitamin D deficiency (VDD) and hypertension, and the association of KD with hypertension and VDD, all of which are associated with an elevated activity of the RAS, provides clues to the pathogenesis of KD. There is increasing evidence implicating embryonic-like stem (ESC) cells that express ESC markers within keloid-associated lymphoid tissues (KALTs) in keloid lesions. These primitive cells express components of the RAS, cathepsins B, D, and G that constitute bypass loops of the RAS, and vitamin D receptor (VDR). This suggests that the RAS directly, and through signaling pathways that converge on the RAS, including VDR-mediated mechanisms and the immune system, may play a critical role in regulating the primitive population within the KALTs. This review discusses the role of the RAS, its relationship with hypertension, vitamin D, VDR, VDD, and the immune system that provide a microenvironmental niche in regulating the ESC-like cells within the KALTs. These ESC-like cells may be a novel therapeutic target for the treatment of this enigmatic and challenging condition, by modulating the RAS using inhibitors of the RAS and its bypass loops and convergent signaling pathways.

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

Cited by 56 publications

References 16 publications

Direct and Indirect Roles of Macrophages in Hypertrophic Scar Formation

Direct and Indirect Roles of Macrophages in Hypertrophic Scar Formation

Characteristics of Tumor Immune Gene and Immune Cell Infiltration during Keloid Formation

The Role of the Renin-Angiotensin System and Vitamin D in Keloid Disorder—A Review

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