title: Inflammatory monocytes recruited to allergic skin acquire an anti-inflammatory M2 phenotype via basophil-derived interleukin-4.
abstract: Monocytes and macrophages are important effectors and regulators of inflammation, and both can be divided into distinct subsets based on their phenotypes. The developmental and functional relationship between individual subsets of monocytes and those of macrophages has not been fully elucidated, although Ly6C(+)CCR2(+) inflammatory and Ly6C(-)CCR2(-) resident monocytes are generally thought to differentiate into M1 (classically activated) and M2 (alternatively activated) macrophages, respectively. Here we show that inflammatory monocytes recruited to allergic skin acquired an M2-like phenotype in response to basophil-derived interleukin-4 (IL-4) and exerted an anti-inflammatory function. CCR2-deficient mice unexpectedly displayed an exacerbation rather than alleviation of allergic inflammation, in spite of impaired recruitment of inflammatory monocytes to skin lesions. Adoptive transfer of inflammatory monocytes from wild-type but not IL-4 receptor-deficient mice dampened the exacerbated inflammation in CCR2-deficient mice. Thus, inflammatory monocytes can be converted from being proinflammatory to anti-inflammatory under the influence of basophils in allergic reactions.
authors: Department of Immune Regulation, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo 113-8519, Japan.
authors: Mayumi
authors: M
authors: Egawa
authors: Kaori
authors: K
authors: Mukai
authors: Soichiro
authors: S
authors: Yoshikawa
authors: Misako
authors: M
authors: Iki
authors: Naofumi
authors: N
authors: Mukaida
authors: Yohei
authors: Y
authors: Kawano
authors: Yoshiyuki
authors: Y
authors: Minegishi
authors: Hajime
authors: H
authors: Karasuyama
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000950:Antigens, Ly; C515335:Ccr2 protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit; C494192:Ly-6C antigen, mouse; D054390:Receptors, CCR2; D015847:Interleukin-4