Effect of leukotriene B4 receptors in dendritic cell function in type 1 diabetes mice model

Abstract

Leukotriene (LT) B4 is a lipid mediator that acts mostly during inflammatory response, enhancing microbial killing, phagocytosis and leukocyte accumulation. LTB4 acts in cells through two receptors, the high affinity BLT-1 and low affinity BLT-2. Both receptors can be found in several cell types, including immunocompetent cells, such as macrophages, neutrophils and dendritic cells. This lipid mediator is also related with type 1 diabetes (T1D), where diabetic mice shows high levels of circulant LTB4, which is also related to maintenance of the Sterile Inflammation state.We already found that LTB4 can act as a maturation stimulus to bone marrow dendritic cells (BM-DCs), inducing CD86 expression and antigen presentation, directing the CD4-positive cells to a phenotypic profile with higher expression of Gata3 and Foxp3. The dendritic cells are the link between innate and adaptive response, and modulating its function is highly relevant to an infection outcome.In this collaboration project, we propose to study the participation of each LTB4 receptor (BLT-1 and BLT-2) in BM-DCs function in both healthy and T1D mice, using a unique strain of genetic modified animals. We also aim to further understands the functional significance of LTB4 in dendritic cells activity in a in vivo model of skin infection with methicillin-resistant Staphylococcus Aureus (MRSA), accessing both the participation of each LTB4 receptor in healthy or T1D infected animals. With this data, we intend to bring to light the modulation that occurs in dendritic cell function in a multifactorial disease as diabetes.