TY - JOUR
T1 - Inflammatory Monocytes Recruited to Allergic Skin Acquire an Anti-inflammatory M2 Phenotype via Basophil-Derived Interleukin-4
AU - Egawa, Mayumi
AU - Mukai, Kaori
AU - Yoshikawa, Soichiro
AU - Iki, Misako
AU - Mukaida, Naofumi
AU - Kawano, Yohei
AU - Minegishi, Yoshiyuki
AU - Karasuyama, Hajime
N1 - Funding Information:
We thank W.A. Kuziel (External Scientific Affairs, Daiichi Sankyo Group, Edison, NJ) for providing Ccr2 −/− mice, D. Yamanaka and R. Matsunaga for technical support, and M. Miki for secretary assistance. This work was supported by a research grant from JST, CREST (to H.K.).
PY - 2013/3/21
Y1 - 2013/3/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875508135&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875508135&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2012.11.014
DO - 10.1016/j.immuni.2012.11.014
M3 - Article
C2 - 23434060
AN - SCOPUS:84875508135
VL - 38
SP - 570
EP - 580
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -