title: Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators.
abstract: Resolution of inflammation is an active process that is mediated in part by antiinflammatory lipid mediators. Although phospholipase A2 (PLA2) enzymes have been implicated in the promotion of inflammation through mobilizing lipid mediators, the molecular entity of PLA2 subtypes acting upstream of antiinflammatory lipid mediators remains unknown. Herein, we show that secreted PLA2 group IID (PLA2G2D) is preferentially expressed in CD11c(+) dendritic cells (DCs) and macrophages and displays a pro-resolving function. In hapten-induced contact dermatitis, resolution, not propagation, of inflammation was compromised in skin and LNs of PLA2G2D-deficient mice (Pla2g2d(-/-)), in which the immune balance was shifted toward a proinflammatory state over an antiinflammatory state. Bone marrow-derived DCs from Pla2g2d(-/-) mice were hyperactivated and elicited skin inflammation after intravenous transfer into mice. Lipidomics analysis revealed that PLA2G2D in the LNs contributed to mobilization of a pool of polyunsaturated fatty acids that could serve as precursors for antiinflammatory/pro-resolving lipid mediators such as resolvin D1 and 15-deoxy-Δ(12,14)-prostaglandin J2, which reduced Th1 cytokine production and surface MHC class II expression in LN cells or DCs. Altogether, our results highlight PLA2G2D as a "resolving sPLA2" that ameliorates inflammation through mobilizing pro-resolving lipid mediators and points to a potential use of this enzyme for treatment of inflammatory disorders.
authors.affiliation: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Miki
authors.forename: Kei
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Taketomi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sato
authors.forename: Kanako
authors.initials: K
authors.lastname: Shimo
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ishii
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.forename: James M
authors.initials: JM
authors.lastname: Bollinger
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000276:immunology / Q000378:metabolism; D054501:Group II Phospholipases A2 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D008055:Lipids / Q000276:immunology*; D008221:Lymphoid Tissue / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010714:Phosphatidylethanolamines / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000201:enzymology / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005231:Fatty Acids, Unsaturated; D007155:Immunologic Factors; D008055:Lipids; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D054501:Group II Phospholipases A2; C516294:Pla2g2d protein, mouse