CCL27-transgenic mice show enhanced contact hypersensitivity to Th2, but not Th1 stimuli.
CCL27 is one of the CC chemokines produced by epidermal keratinocytes and is suggested to be involved in the pathogenesis of inflammatory skin diseases. To clarify the contribution of CCL27 in skin inflammation, we created transgenic C57BL/6 mice that constitutively produce CCL27 in epidermal keratinocytes. These mice had high serum CCL27 levels and did not show any phenotypical change. Thus we stimulated these mice with various reagents by single and repeated application. Interestingly, only contact hypersensitivity to repeated application with fluorescein isothiocyanate was significantly enhanced in transgenic mice compared to non-transgenic mice. Under this condition, the numbers of inflammatory cells, CCR10-positive cells, CCR4-positive cells and cutaneous lymphocyte-associated antigen-positive cells were increased, and IL-4 mRNA expression was higher in the lesional skin of transgenic mice. Increased number of mast cells and higher serum IgE levels, which were similar to atopic dermatitis, were also observed. These results indicated that CCL27 modified inflammation by attracting CCR10-positive and CCR4-positive cells into the lesional skin, and may participate in the pathogenesis of Th2-shifted skin diseases such as atopic dermatitis.
Kagami
Shinji
S
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. kagamis-tky@umin.ac.jp
Saeki
Hidehisa
H
Tsunemi
Yuichiro
Y
Nakamura
Koichiro
K
Kuwano
Yoshihiro
Y
Komine
Mayumi
M
Nakayama
Takashi
T
Yoshie
Osamu
O
Tamaki
Kunihiko
K
D000818:Animals; D002452:Cell Count; D054425:Chemokine CCL27 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007114:Immunization / Q000379:methods; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010081:Oxazolone / Q000276:immunology / Q000494:pharmacology; D054447:Receptors, CCR10 / Q000032:analysis; D054398:Receptors, CCR4 / Q000032:analysis; D012867:Skin / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
C119538:Ccl27a protein, mouse; C515707:Ccr10 protein, mouse; C515355:Ccr4 protein, mouse; D054425:Chemokine CCL27; D017077:Culture Media, Conditioned; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D010081:Oxazolone; D015847:Interleukin-4; D007073:Immunoglobulin E