Effects of oleic acid on the origin and functions of monocytes and macrophages in skin IMQ-induced psoriasis mouse model

Abstract

Skin forms a barrier that protect the body from external environment through physical and immunological functions. Dysregulation of immune reactions in skin can contribute to inflammatory skin disorders, such as psoriasis. Keratinocytes are activated through pattern recognition receptors (PRRs) making them a source of interleukins (IL)-1², IL-6, IL-10 , tumor necrosis factor alpha (TNF-±), chemokines such as CXCL8, CXCL10 and antimicrobial proteins (²-defensins and cathelicidins). These mediators induce migrations of neutrophils and monocytes. Understanding about origin and functions of monocytes and macrophages in skin is essential to therapeutic advances psoriasis. So, the first aim of this work is to investigate the origin of monocytes/macrophages that populate skin on IMQ-induced psoriasis mouse model. For that, we will do transplantation of CD45.1+ bone marrow (BM) into lethally irradiated CD45.2+ recipients. After two months of transplantation CD45.2+ will be treated with vaselin (control mice) or imiquimode (IMQ) for 3 days. At the 3rd day, mice will be euthanized, and skin will be processed to flow cytometry and expression of CD45.1, and lack of CD45.2 expression will be used to assess proper BM engraftment. This model is often used for in vivo tracking of immune cell development. After that, considering that oral supplementation with oleic acid reduces inflammatory response in psoriasis mouse model, the second step will be investigated effects of oleic acid on functions of monocytes/macrophages isolated from skin or bone-marrow by RNA sequencing. These results will contribute to understanding the effects of oleic fatty acids on the attenuation of IMQ-induced psoriasis in mouse model and promote therapeutic advances.