Project description:TH2 and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as IL4, IL5 and IL13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment (TME) are unknown. Here, in pancreatic ductal adenocarcinoma (PDAC), we show that oncogenic KrasG12D (Kras*) increases the expression of IL33 in cancer cells, which upon secretion recruits and activates the TH2 and ILC2. Correspondingly, cancer cell-specific deletion of IL33 reduces TH2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, we discovered that the cellular release of IL33 into the TME is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL33 or anti-fungal treatment decreases TH2 and ILC2 infiltration and increases survival. Consistent with these murine data, high IL33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identifies therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL33.
Project description:We report the RNAseq of mouse pancreatic cancer cell lines with Kras ON vs Kras OFF. TH2 and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as IL4, IL5 and IL13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment (TME) are unknown. Here, in pancreatic ductal adenocarcinoma (PDAC), we show that oncogenic KrasG12D (Kras*) increases the expression of IL33 in cancer cells, which upon secretion recruits and activates the TH2 and ILC2. Correspondingly, cancer cell-specific deletion of IL33 reduces TH2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, we discovered that the cellular release of IL33 into the TME is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL33 or anti-fungal treatment decreases TH2 and ILC2 infiltration and increases survival. Consistent with these murine data, high IL33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identifies therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL33.
Project description:Understanding the microbial community structure of human skin is important for treating cutaneous diseases; however, there is little known about skin fungal communities (mycobiome). This was investigated in the present study by examining the features of and variations in skin fungal communities during infancy in 110 subjects under 6 months old. Skin samples were obtained from the back, antecubital fossa, and volar forearm, and physiological parameters including transepidermal water loss, pH, surface moisture, and deep layer hydration were evaluated. Skin fungal diversity decreased after the first 3 months of life.
Project description:Understanding the microbial community structure of human skin is important for treating cutaneous diseases; however, there is little known about skin fungal communities (mycobiome). This was investigated in the present study by examining the features of and variations in skin fungal communities during infancy in 110 subjects under 6 months old. Skin samples were obtained from the back, antecubital fossa, and volar forearm, and physiological parameters including transepidermal water loss, pH, surface moisture, and deep layer hydration were evaluated. Skin fungal diversity decreased after the first 3 months of life.
Project description:Comparison of gene expression level by Illumina sequencing of rat skin from young and old animals. We identified differentially expressed genes and provide functional profiles, which give insights into the aging process of short-lived rodents.
Project description:Radiation dermatitis is a side effect in cancer radiotherapy, where ionizing radiation is delivered to eradicate cancer. Normal tissue such as the skin is also damaged by this treatment. We report here the gene expression change in a rat footpad model of this disease.