Exploring the roles of prostanoids, leukotriens, and dietary fatty acids in cutaneous inflammatory diseases: Insights from pharmacological and genetic approaches

Author:

Honda Tetsuya1,Kabashima Kenji234ORCID,Kunisawa Jun56789

Affiliation:

1. Department of Dermatology Hamamatsu University School of Medicine Hamamatsu Japan

2. Department of Dermatology Kyoto University Graduate School of Medicine Kyoto Japan

3. Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), Biopolis Singapore Singapore

4. 5. A*Star Skin Research Labs (A*SRL), Agency for Science, Technology, and Research (A*STAR), Biopolis Singapore Singapore

5. Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, Collaborative Research Center for Health and Medicine National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN) Osaka Japan

6. International Vaccine Design Center The Institute of Medical Science, The University of Tokyo Tokyo Japan

7. Graduate School of Medicine, Graduate School of Dentistry, Graduate School of Pharmaceutical Sciences, Graduate School of Science Osaka University Osaka Japan

8. Department of Microbiology and Immunology, Graduate School of Medicine Kobe University Kobe Japan

9. Research Organization for Nano and Life Innovation Waseda University Tokyo Japan

Abstract

SummaryProstanoids and leukotrienes (LTs) are representative of ω6 fatty acid‐derived metabolites that exert their actions through specific receptors on the cell surface. These lipid mediators, being unstable in vivo, act locally at their production sites; thus, their physiological functions remain unclear. However, recent pharmacological and genetic approaches using experimental murine models have provided significant insights into the roles of these lipid mediators in various pathophysiological conditions, including cutaneous inflammatory diseases. These lipid mediators act not only through signaling by themselves but also by potentiating the signaling of other chemical mediators, such as cytokines and chemokines. For instance, prostaglandin E2‐EP4 and LTB4‐BLT1 signaling on cutaneous dendritic cells substantially facilitate their chemokine‐induced migration ability into the skin and play critical roles in the priming and/or activation of antigen‐specific effector T cells in the skin. In addition to these ω6 fatty acid‐derived metabolites, various ω3 fatty acid‐derived metabolites regulate skin immune cell functions, and some exert potent anti‐inflammatory functions. Lipid mediators act as modulators of cutaneous immune responses, and manipulating the signaling from lipid mediators has the potential as a novel therapeutic approach for human skin diseases.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

Subject

Immunology,Immunology and Allergy

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