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発表内容

Title:

Leukotriene B4 receptors in host defense response

 

Tomoaki Koga

Assistant Professor

Higo, Leading Graduate Schools, Kumamoto university

 

Abstract:

Leukotriene B4 (LTB4) is a classical inflammatory LIPID mediator produced from leukocytes. LTB4 activates and recruits various inflammatory cells including neutrophils and macrophages. LTB4 is recognized by two receptors, BLT1 and BLT2. BLT1 is expressed mainly in blood cells, whereas BLT2 is expressed mainly in epithelial cells. Both receptors are involved in host defense responses, but in different ways. In this presentation, I would like to talk about recent progress about the roles of BLT1 and BLT2 in host immune responses.
Firstly, I will talk about the role of BLT1 in dendritic cells (DCs). DCs are highly specialized antigen-presenting cells (APCs) that regulate various immune responses by releasing cytokines and interacting with T cells. Although we reported BLT1 accelerates Th1-dependent contact dermatitis, Th2-dependent allergic asthma, and Th17-dependent experimental autoimmune encephalomyelitis by using BLT1-deficient mice, the roles of BLT1 in dendritic cells are still largely unknown. Here, we describe distinct subsets of DCs characterized by expression levels of BLT1, namely BLT1hi and BLT1lo DCs. BLT1hi DCs preferentially increased IL-12p35 expression and induced Th1 differentiation. On the other hand, BLT1lo DCs had higher potential to migrate toward lymph nodes and accelerated T cell proliferation in vitro and in vivo. These subsets might manipulate various immune responses.
Secondly, I will talk about the role of BLT2 in acute lung injury (ALI). Pneumococcal infection is still a serious problem worldwide and has a high mortality rate. However, the molecular mechanisms underlying the lethality caused by pneumocoocus remains largely elusive. In this study, we showed that BLT2 protects against lethal ALI caused by pneumococcal toxin pneumolysin. As a mechanism, we found that BLT2 controls CysLT1 signaling, which accelerates vascular leakage and bronchoconstriction. These data suggests the possible use of CysLT1 antagonists as therapeutic tools to protect against ALI caused by pneumococcal infection.
In summary, I describe the distinct roles of leukotriene B4 receptors in host defense response and would like to introduce the lipid mediators that are, of course, not encoded to genome in this presentation.