title: SOCS3 Expressed in M2 Macrophages Attenuates Contact Hypersensitivity by Suppressing MMP-12 Production.
abstract: Numerous studies have clarified the immunological mechanisms of contact hypersensitivity (CHS). In addition, we have recently shown that M2 macrophages play key roles in the development of CHS by producing matrix metalloproteinase-12 (MMP-12). However, regulatory mechanisms of the elicitation phase in CHS remain largely unknown. To determine the roles of suppressor of cytokine signaling (SOCS) family members in M2 macrophages in the regulation of CHS, we investigated the expression of SOCS family members in M2 macrophages at the inflammatory sites of CHS. Transcriptome analysis revealed that among SOCS family members, SOCS3 was highly expressed in M2 macrophages at the site of CHS, and SOCS3 induction was reduced by IFN-? neutralization. 2,4-Dinitrofluorobenzene-induced CHS was significantly enhanced and prolonged in mice lacking SOCS3 expression in monocytes/macrophages (SOCS3(?/?) mice) compared with that in control mice. Importantly, expression of MMP-12 in M2 macrophages was significantly increased in SOCS3(?/?) mice at the site of CHS, and deletion of the MMP-12 gene reduced the exacerbated CHS in SOCS3(?/?) mice. Finally, IFN-? inhibited IL-4-induced MMP-12 expression in a SOCS3-dependent manner. Taken together, these results suggest that SOCS3 expressed in M2 macrophages is involved in the attenuation and/or resolution of CHS, presumably by suppressing MMP-12 production.
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Meguro
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Nakagomi
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address: suzuki_k@faculty.chiba-u.jp.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hosokawa
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Fukuta
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yokota
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Maezawa
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Suto
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address: nakajimh@faculty.chiba-u.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053508:Matrix Metalloproteinase 12