title: Eosinophils control the resolution of inflammation and draining lymph node hypertrophy through the proresolving mediators and CXCL13 pathway in mice.
abstract: Resolution of inflammation is critical to restoration of tissue function after an inflammatory response. We previously demonstrated that 12/15-lipoxygenase (12/15-LOX)-expressing eosinophils contribute to this process in murine zymosan-induced peritonitis. In this study, eosinophils promoted resolution by regulating expression of macrophage CXCL13. Microarray analysis revealed that eosinophils significantly increased (∼3-fold) the expression of macrophage CXCL13 by a 12/15-LOX-dependent mechanism. CXCL13 depletion caused a resolution defect, with the reduced appearance of phagocytes carrying engulfed zymosan in the draining lymph nodes. Inflamed lymph node hypertrophy, a critical feature of the resolution process, was reduced by ∼60% in eosinophil-deficient mice, and adoptive transfer of eosinophils or administration of CXCL13 corrected this defect. Administration of the 12/15-LOX-derived mediator lipoxin A4 (LXA4) increased the expression of CXCL13 and restored the defect of lymph node hypertrophy in eosinophil-deficient mice. These results demonstrate that eosinophils control the resolution of inflammation and draining lymph node hypertrophy through proresolving lipid mediators and the CXCL13 pathway in mice.
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Tokyo, Japan;
authors.forename: Yukako
authors.initials: Y
authors.lastname: Tani
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Tokyo, Japan; Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan;
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Isobe
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; and.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Imoto
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; and.
authors.forename: Eri
authors.initials: E
authors.lastname: Segi-Nishida
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Tokyo, Japan;
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Tokyo, Japan; Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japanese Science and Technology Agency, Saitama, Japan; marita@mol.f.u-tokyo.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D006984:Hypertrophy; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D044045:Lipoxins / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D010538:Peritonitis / Q000378:metabolism / Q000473:pathology*
chemical_list: C475064:12-15-lipoxygenase; D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; D044045:Lipoxins; C040527:lipoxin A4; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase
keywords: lipid mediator; lipoxygenase