Toll‐Like Receptor 7 (TLR7) Mediated Transcriptomic Changes on Human Mast Cells

Background@#Mast cells are skin immune sentinels located in the upper dermis, where wheal formation and sensory nerve stimulation take place. Skin inflammation is occasionally accompanied by mast cell-driven responses with wheals, angioedema, or both. Immunoglobulin E (IgE) antibodies are regarded as typical stimuli to drive mast cell activation. However, various causative factors, including microbial infections, can drive IgE-independent mast cell response. When infected, the innate immunity orchestrates an immune response by activating receptor signaling via Toll-like receptors (TLRs). @*Objective@#In this study, we determined the effect of TLR7 stimulation on mast cells to investigate the possible mechanism of IgE-independent inflammatory response. @*Methods@#Human mast cell (HMC) line, HMC-1 cells were treated with TLR7 agonist and the morphologic alteration was observed in transmission electron microscopy. Further, TLR7 agonist treated HMC-1 cells were conducted to RNA sequencing to compare transcriptomic features. @*Results@#HMC-1 cells treated with TLR7 agonist reveals increase of intracellular vesicles, lipid droplets, and ribosomes. Also, genes involved in pro-inflammatory responses such as angiogenesis are highly expressed, and Il12rb2 was the most highly upregulated gene. @*Conclusion@#Our data suggest that TLR7 signaling on mast cells might be a potential therapeutic target for mast cell-driven, IgE-independent skin inflammation.

Toll‐Like Receptor 7 (TLR7) Mediated Transcriptomic Changes on Human Mast Cells

Background@#Mast cells are skin immune sentinels located in the upper dermis, where wheal formation and sensory nerve stimulation take place. Skin inflammation is occasionally accompanied by mast cell-driven responses with wheals, angioedema, or both. Immunoglobulin E (IgE) antibodies are regarded as typical stimuli to drive mast cell activation. However, various causative factors, including microbial infections, can drive IgE-independent mast cell response. When infected, the innate immunity orchestrates an immune response by activating receptor signaling via Toll-like receptors (TLRs). @*Objective@#In this study, we determined the effect of TLR7 stimulation on mast cells to investigate the possible mechanism of IgE-independent inflammatory response. @*Methods@#Human mast cell (HMC) line, HMC-1 cells were treated with TLR7 agonist and the morphologic alteration was observed in transmission electron microscopy. Further, TLR7 agonist treated HMC-1 cells were conducted to RNA sequencing to compare transcriptomic features. @*Results@#HMC-1 cells treated with TLR7 agonist reveals increase of intracellular vesicles, lipid droplets, and ribosomes. Also, genes involved in pro-inflammatory responses such as angiogenesis are highly expressed, and Il12rb2 was the most highly upregulated gene. @*Conclusion@#Our data suggest that TLR7 signaling on mast cells might be a potential therapeutic target for mast cell-driven, IgE-independent skin inflammation.

Conditioned Medium from Tonsil-Derived Mesenchymal Stem Cells Relieves CCl₄-Induced Liver Fibrosis in Mice

BACKGROUND: The liver is an organ with remarkable regenerative capacity; however, once chronic fibrosis occurs, liver failure follows, with high mortality and morbidity rates. Continuous exposure to proinflammatory stimuli exaggerates the pathological process of liver failure; therefore, immune modulation is a potential strategy to treat liver fibrosis. Mesenchymal stem cells (MSCs) with tissue regenerative and immunomodulatory potential may support the development of therapeutics for liver fibrosis. METHODS: Here, we induced hepatic injury in mice by injecting carbon tetrachloride (CCl₄) and investigated the therapeutic potential of conditionedmedium from tonsil-derivedMSCs (T-MSCCM). In parallel, we used recombinant human IL-1Ra,which, as we have previously shown, is secreted exclusively from T-MSCs and resolves the fibrogenic activation of myoblasts. Hepatic inflammation and fibrosis were determined by histological analyses using H&E and Picro-Sirius Red staining. RESULTS: The results demonstrated that T-MSC CM treatment significantly reduced inflammation as well as fibrosis in the CCl₄-injured mouse liver. IL-1Ra injection showed effects similar to T-MSC CM treatment, suggesting that T-MSC CM may exert anti-inflammatory and anti-fibrotic effects via the endogenous production of IL-1Ra. The expression of genes involved in fibrosis was evaluated, and the results showed significant induction of alpha-1 type I collagen, transforming growth factor beta, and tissue inhibitor of metalloproteases 1 upon CCl₄ injection, whereas treatment with T-MSC CM or IL-1Ra downregulated their expression. CONCLUSION: Taken together, these data support the therapeutic potential of T-MSC CM and/or IL-1Ra for the alleviation of liver fibrosis, as well as in treating diseases involving organ fibrosis.

Mast Cells and Microbiome in Skin Immunity

The skin functions as a physical barrier against entry of pathogens while concomitantly supporting a myriad of commensal organisms. The characterization of these microbial communities has enhanced our knowledge of the ecology of organisms present in normal skin, and studies have begun to illuminate the intimate relationship between the host and resident microbes. The cutaneous innate and adaptive immune responses can modulate skin microbiota, while simultaneously, the microbiota educates the host immune system. A crucial element of the innate immune response is mast cells, which reside strategically in tissues that are commonly exposed to the external environment, such as the skin and mucosae. Mast cells are present on the frontline of defense against pathogens, suggesting they may play an important role in fostering the host-microbiota relationship. In this review, we highlight findings regarding the interaction between skin microbiota and mast cells and the resulting outcomes in skin homeostasis.

Mast Cells and Microbiome in Skin Immunity

The skin functions as a physical barrier against entry of pathogens while concomitantly supporting a myriad of commensal organisms. The characterization of these microbial communities has enhanced our knowledge of the ecology of organisms present in normal skin, and studies have begun to illuminate the intimate relationship between the host and resident microbes. The cutaneous innate and adaptive immune responses can modulate skin microbiota, while simultaneously, the microbiota educates the host immune system. A crucial element of the innate immune response is mast cells, which reside strategically in tissues that are commonly exposed to the external environment, such as the skin and mucosae. Mast cells are present on the frontline of defense against pathogens, suggesting they may play an important role in fostering the host-microbiota relationship. In this review, we highlight findings regarding the interaction between skin microbiota and mast cells and the resulting outcomes in skin homeostasis.

Inflammation in Obesity

Obesity that caused by high-fat diet, heredity, drinking, or lack of exercise is related to metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular disease and it becomes a serious social problem. Although obesity shows low-grade chronic inflammation which induces from immune response in adipose tissue, relation between inflammation and pathogenesis of obesity has not been incompletely understood. Therefore, study for immune response in obesity is essential to design effective therapeutic strategy.