Lymphoid tissue phospholipase A(2) group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators

作者：Miki Yoshimi; Yamamoto Kei; Taketomi Yoshitaka; Sato Hiroyasu; Shimo Kanako; Kobayashi Tetsuyuki; Ishikawa Yukio; Ishii Toshiharu; Nakanishi Hiroki; Ikeda Kazutaka; Taguchi Ryo; Kabashima Kenji; Arita Makoto; Arai Hiroyuki; Lambeau Gerard; Bollinger James M; Hara Shuntaro; Gelb Michael H; Murakami Makoto^*

来源：Journal of Experimental Medicine, 2013, 210(6): 1217-1234.

DOI：10.1084/jem.20121887

Resolution of inflammation is an active process that is mediated in part by antiinflammatory lipid mediators. Although phospholipase A(2) (PLA(2)) enzymes have been implicated in the promotion of inflammation through mobilizing lipid mediators, the molecular entity of PLA(2) subtypes acting upstream of antiinflammatory lipid mediators remains unknown. Herein, we show that secreted PLA(2) 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-Delta(12,14)-prostaglandin J(2), which reduced Th1 cytokine production and surface MHC class II expression in LN cells or DCs. Altogether, our results highlight PLA2G2D as a %26quot;resolving sPLA(2)%26quot; that ameliorates inflammation through mobilizing pro-resolving lipid mediators and points to a potential use of this enzyme for treatment of inflammatory disorders.

• 出版日期2013-6-3
• 单位河北医科大学