1849-PUB: RNA Sequencing Analysis Related to Immune Homeostasis in the Skin of a Corticotropin-Releasing Hormone (CRH) Transgenic Mouse Model

Chronic glucocorticoid exposure in humans is well-known to induce diabetes-like phenotypes associated with Cushing's syndrome. Diabetes mellitus is also closely related to skin abnormalities. To elucidate changes in the transcriptome of the skin in corticotrophin-releasing hormone transgenic (CRH-TG) mice with skin abnormalities and diabetes-like phenotypes, we performed RNA-Seq analysis with a focus on immune homeostasis. Compared to WT-skin, DEG analysis revealed that the levels of 2854 genes were significantly altered in CRH-TG mice (Up-1134 genes, Down-1720 genes). The KEGG analysis further showed that various signaling pathways associated with immune functions were significantly altered, which include signaling pathways related to hematopoietic cells, complement cascade, and major histocompatibility complex class II (MHC class II) molecules. Additionally, qPCR analysis confirmed that the mRNA level of MHC class II molecules, which play an antigen-presenting function, was downregulated in CRH-TG skin. Although further studies are needed, chronic glucocorticoid exposure may lead to immune imbalance, making the skin vulnerable to external and intrinsic stimulations.