Roles of alternatively activated M2 macrophages in allergic contact dermatitis.
Alternatively activated macrophages (M2 macrophages) play key roles in the suppression of Th1 cell responses and the orchestration of tissue repair. However, recent studies have shown that M2 macrophages have potentials to produce high levels of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α, suggesting that M2 macrophages may exacerbate inflammation in some settings. In this regard, we have recently shown that large numbers of M2 macrophages accumulate in the sites of hapten-induced contact hypersensitivity (CHS), an animal model of allergic contact dermatitis, and that M2 macrophages exacerbate hapten-induced CHS by producing matrix metalloproteinase 12 (MMP12). We have also shown that suppressor of cytokine signaling-3 (SOCS3), a member of SOCS family proteins that are cytokine-inducible negative regulators of the JAK/STAT signaling pathways, is highly and preferentially expressed in M2 macrophages in hapten-induced CHS and that SOCS3 expressed in M2 macrophages is involved in the attenuation of CHS by suppressing MMP12 production. These findings underscore the importance of M2 macrophage-derived MMP12 in the development of CHS, and suggest that inhibition of M2 macrophages or MMP12 could be a potential therapeutic strategy for the treatment of allergic contact dermatitis.
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address: suzuki_k@faculty.chiba-u.jp.
Kotaro
K
Suzuki
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kazuyuki
K
Meguro
Department of Third Internal Medicine, University of Yamanashi, Yamanashi, Japan.
Daiki
D
Nakagomi
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hiroshi
H
Nakajima
D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000009:adverse effects; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D000071223:Suppressor of Cytokine Signaling 3 Protein; D004139:Dinitrofluorobenzene; D053508:Matrix Metalloproteinase 12
Contact hypersensitivity; M2 macrophages; MMP12; SOCS3; mannose receptor