Interleukin (IL)-7 plays a vital role in proliferation and activation of T cells, however, its signaling through CD127 is impaired in T cells in cancers and chronic infections. The mechanisms underlying T helper 17 (Th17) cell responses by IL-7 in melanoma remain not fully understood. The aim of this study was to assess the effect of IL-7 signaling on Th17 responses in patients with primary cutaneous melanoma. Healthy and primary cutaneous melanoma donors were selected for this study of Th17 cell function. IL-17 + CD4 + Th17 cells and CD127 expression on Th17 cells were determined by flow cytometry. Cytokine level was measured by ELISA. Peripheral and tissueinfiltrating CD4 + T cells were isolated using magnetic beads, and then stimulated with IL-7 and/or signal transducer and activator of transcription 5 inhibitor. Activated signaling molecules were analyzed by flow cytometry. Peripheral and tumor-infiltrating Th17 cells percentage was decreased, while peripheral IL-7 level was also reduced in melanoma patients. There was no significant difference of CD127 expression on Th17 cells between melanoma patients and controls. Antiapoptotic protein Bcl-2 was downregulated, whereas proapoptotic protein-activated caspase-3 was upregulated in peripheral and tissue-infiltrating Th17 cells in melanoma patients.Higher concentration of IL-7 (10 ng/mL), but not lower IL-7 concentration (1 ng/mL), promoted Bcl-2 expression and decreased caspase-3 expression in Th17 cells in melanoma patients. Inhibition of signal transducer and activator of transcription 5 resulted in the downregulation of Bcl-2 while upregulation of caspase-3 in Th17 cells. The present data suggested that reduced IL-7 responsiveness might be insufficient for Th17 activation in patients with primary cutaneous melanoma.
Background Interleukin (IL)-7 signaling through CD127 is impaired in lymphocytes in cancers and chronic infections, resulting in CD8+ T cell exhaustion. The mechanisms underlying CD8+ T cell responses to IL-7 in melanoma remain not completely elucidated. We previously showed reduced IL-7 level in melanoma patients. Thus, the aim of this study was to investigate the effect of IL-7 regulation on CD127 expression and CD8+ T cell responses in melanoma. Methods Healthy controls and primary cutaneous melanoma patients were enrolled. Membrane-bound CD127 (mCD127) expression on CD8+ T cells was determined by flow cytometry. Soluble CD127 (sCD127) protein level was measured by ELISA. Total CD127 and sCD127 mRNA level was measured by real-time PCR. CD8+ T cells were stimulated with recombinant human IL-7, along with signaling pathway inhibitors. CD8+ T cells were co-cultured with melanoma cell line, and the cytotoxicity of CD8+ T cells was assessed by measurement of lactate dehydrogenase expression. Results Plasma sCD127 was lower in melanoma patients compared with controls. The percentage of CD8+ T cells expressing mCD127 was higher, while sCD127 mRNA level was lower in peripheral and tumor-infiltrating CD8+ T cells from melanoma patients. There was no significant difference of total CD127 mRNA expression in CD8+ T cells between groups. IL-7 stimulation enhanced total CD127 and sCD127 mRNA expression and sCD127 release by CD8+ T cells. However, mCD127 mRNA expression on CD8+ T cells was not affected. This process was mainly mediated by phosphatidylinositol 3-kinase (PI3K) pathway. CD8+ T cells from melanoma patients exhibited decreased cytotoxicity. IL-7 stimulation promoted CD8+ T cell cytotoxicity, while inhibition of PI3K dampened IL-7-induced elevation of CD8+ T cell cytotoxicity. Conclusion The current data suggested that insufficient IL-7 secretion might contribute to CD8+ T cell exhaustion and CD127 dysregulation in patients with primary cutaneous melanoma.
Hypertrophic scar (HS) is a process of tissue repair and healing, and excessive fibrosis of local tissue leads to scar formation. During HS formation, fibroblasts (Fb) proliferate, synthesize and secrete and promote HS development. miR-184 regulates skin formation and tissue development. However, miR-184’s role in HS remains unclear. miR-184 expression in HS patients and normal healthy (Control) tissues was measured by real-time PCR. pAKT expression was analyzed by Western blot. Fb cells from human HS were cultured and divided into 2 groups, siRNA NC group and miR-184 siRNA group followed by analysis of miR-184 expression by real time PCR, cell proliferation by MTT assay, secretion of inflammatory factors IL-1β and IL-6 by ELISA, as well as expression of pAKT and AKT by western blot. Compared with control group, miR-184 and pAKT expression was significantly increased in the HS group. Transfection of miR-184 siRNA into Fb significantly downregulated miR-184 expression, inhibited cell proliferation, promoted Caspase 3 activity, decreased IL-1β and IL-6 secretion, and reduced pAKT level (P < 0.05). miR-184 expression is increased in hypertrophic scar tissue. Down-regulation of miR-184 expression in proliferative scar tissue fibroblasts can down-regulate PI3K/AKT signaling pathway, inhibit inflammation, promote apoptosis, inhibit fibroblast proliferation, and regulate hypertrophic scar formation.
Epidermolytic acanthoma (EA) is a rare benign tumor that is characterized by epidermolytic hyperkeratosis on histopathology. It usually presents in adulthood as an asymptomatic tumor <1 cm in diameter with a verrucous surface. We report a very uncommon case of epidermolytic acanthoma. A 21-year-old woman came to our hospital with a pale black papule on the left lower eyelid near the Inner canthus for 2 months. Two months ago the patient noted a pale brown spot on the inside of the left lower eyelid, which gradually enlarged, forming a papule with a deepened color. There were no associated symptoms, such as itching or pain. There were no local injuries, scratches, or other incidents before the crash occurred. The patient was always healthy, with no history of chronic disease or other skin diseases, and no similar cases existed in the family. We diagnosed it as EA.
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