ABSTRACT
There is increasing evidence of the relevant connection and regulation between the gut and skin immune axis. In fact, oral administration of lipoteichoic acid (LTA) from Lactobacillus rhamnosus GG (LGG) prevents the development of UV-induced skin tumors in chronically exposed mice. Here we aim to evaluate whether this LTA is able to revert UV-induced immunosuppression as a mechanism involved in its anti-tumor effect and whether it has an immunotherapeutic effect against cutaneous squamous cell carcinoma. Using a mouse model of contact hypersensitivity, we demonstrate that LTA overcomes UV-induced skin immunosuppression. This effect was in part achieved by modulating the phenotype of lymph node resident dendritic cells (DC) and the homing of skin migratory DC. Importantly, oral LTA reduced significantly the growth of established skin tumors once UV radiation was discontinued, demonstrating that it has a therapeutic, besides the already demonstrated preventive antitumor effect. The data presented here strongly indicates that oral administration of LTA represents a promising immunotherapeutic approach for different conditions in which the skin immune system is compromised.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/drug therapy , Lacticaseibacillus rhamnosus/chemistry , Lipopolysaccharides/pharmacology , Skin Neoplasms/drug therapy , Teichoic Acids/pharmacology , Ultraviolet Rays/adverse effects , Administration, Oral , Animals , Antineoplastic Agents/isolation & purification , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Cell Movement/drug effects , Cell Movement/immunology , Cell Movement/radiation effects , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dendritic Cells/pathology , Dendritic Cells/radiation effects , Dermatitis, Contact/genetics , Dermatitis, Contact/immunology , Dermatitis, Contact/pathology , Female , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/immunology , Gastrointestinal Tract/pathology , Gastrointestinal Tract/radiation effects , Lipopolysaccharides/isolation & purification , Lymph Nodes/drug effects , Lymph Nodes/immunology , Lymph Nodes/pathology , Lymph Nodes/radiation effects , Mice , Mice, Inbred C57BL , Skin/drug effects , Skin/immunology , Skin/pathology , Skin/radiation effects , Skin Neoplasms/genetics , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Teichoic Acids/isolation & purificationABSTRACT
BACKGROUND DATA: Light emitting diode (LED) therapy has been proposed as an option for the treatment of many skin inflammatory processes. Dendritic cells (DCs) are important cells of skin that participate in the initiation and activation of skin immunity. The modulation of these cells by LED could explain much of its effects. OBJECTIVE: Thus, the aim of this study was to examine the effects of LED at 460 ± 20 nm on cytokine production and the expression of surface markers on DCs. MATERIALS AND METHODS: DCs were obtained from mouse bone marrow-derived dendritic cells (BMDCs). The LED was applied giving a fluence of 3.3, 8.2, or 16.5 J/cm2 on BMDCs or lipopolysaccharide (LPS)-matured BMDCs. The production of cytokine was analyzed by enzyme linked immunosorbant assay (ELISA) and the expression of DC co- and stimulatory was analyzed markers by cytometry. RESULTS: LED increases IL-12p40 and IL-6 production in both nonstimulated BMDCs and LPS-matured BMDCs. The expression of MHC-II molecule was inhibited and the expression of the CD86 molecule was increased in nonstimulated BMDCs but not in LPS-matured BMDCs. The production of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) and the expression of CD40 were not altered. CONCLUSIONS: These results demonstrate that LED stimulated cytokine production in BMDCs, suggesting a proinflammatory role in the tested conditions and maybe it can increase DC maturation.