Z Chen1, L Zhou2, T Won1, Z Gao1, X Wu1, L Lu3. 1. Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. 2. Research Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China. 3. Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Abstract
BACKGROUND: Memory T cells, a highly effective subset of T lymphocytes, have been reported to be involved in many inflammatory skin disorders. However, the potential role of memory T cells in keloid disease (KD) remains unclear. OBJECTIVES: Due to their important role in regulating inflammation, we investigated the characteristics of CD45RO+ memory T cells in KD. METHODS: Primary cutaneous cells were isolated from keloid scars and normal skin by enzymic digestion. Peripheral blood mononuclear cells were isolated from a related blood sample, and flow cytometry was applied to identify the phenotypic and functional abnormalities of memory T cells in KD. RESULTS: We observed that the majority of T lymphocytes in keloid scars had the memory phenotype, and a greater number of the CD8+ memory T cells in keloid scars produced lower levels of tumour necrosis factor (TNF)-α. This abnormal cytokine production was even more distinct in Forkhead box (FOX)P3- CD8- memory T cells, with lower TNF-α production and enhanced interferon-γ production. Furthermore, FOXP3+ CD8- memory T cells in keloid scars were abnormal, including showing reduced CD25 and cytotoxic T-lymphocyte-associated antigen 4 expression and interleukin-10 production. In addition, a significant decrease in the number of CD4+ CD25high FOXP3+ regulatory T cells was identified in patients with multiple keloid scars. We also found that there was significantly increased infiltration of CD103+ CD8+ memory T cells in keloid scars. CONCLUSIONS: Our findings preliminarily elucidate the abnormalities of CD45RO+ memory T cells in keloid scars and provide early evidence that a disrupted T-cell response contributes to the progression of KD.
BACKGROUND: Memory T cells, a highly effective subset of T lymphocytes, have been reported to be involved in many inflammatory skin disorders. However, the potential role of memory T cells in keloid disease (KD) remains unclear. OBJECTIVES: Due to their important role in regulating inflammation, we investigated the characteristics of CD45RO+ memory T cells in KD. METHODS: Primary cutaneous cells were isolated from keloid scars and normal skin by enzymic digestion. Peripheral blood mononuclear cells were isolated from a related blood sample, and flow cytometry was applied to identify the phenotypic and functional abnormalities of memory T cells in KD. RESULTS: We observed that the majority of T lymphocytes in keloid scars had the memory phenotype, and a greater number of the CD8+ memory T cells in keloid scars produced lower levels of tumour necrosis factor (TNF)-α. This abnormal cytokine production was even more distinct in Forkhead box (FOX)P3- CD8- memory T cells, with lower TNF-α production and enhanced interferon-γ production. Furthermore, FOXP3+ CD8- memory T cells in keloid scars were abnormal, including showing reduced CD25 and cytotoxic T-lymphocyte-associated antigen 4 expression and interleukin-10 production. In addition, a significant decrease in the number of CD4+ CD25high FOXP3+ regulatory T cells was identified in patients with multiple keloid scars. We also found that there was significantly increased infiltration of CD103+ CD8+ memory T cells in keloid scars. CONCLUSIONS: Our findings preliminarily elucidate the abnormalities of CD45RO+ memory T cells in keloid scars and provide early evidence that a disrupted T-cell response contributes to the progression of KD.
Authors: Jiaheng Xie; Liang Chen; Yuan Cao; Dan Wu; Wenwen Xiong; Kai Zhang; Jingping Shi; Ming Wang Journal: Front Immunol Date: 2021-12-22 Impact factor: 7.561