CCL27 is a critical factor for the development of atopic dermatitis in the keratin-14 IL-4 transgenic mouse model.
The keratin-14 IL-4 transgenic (Tg) mouse model of atopic dermatitis (AD) is characterized by skin infiltration of T cells, early up-regulation of T(h)2 cytokines and late surge of T(h)1 cytokines. In the present study, we investigated the role of CCL27, a T cell skin-homing chemokine known to be elevated in sera of human AD patients, in disease development in our animal model of AD. The results showed that the mRNA and protein levels of CCL27 in the skin and serum were significantly increased in IL-4 Tg mice. The percentage of T cells expressing CCR10 in skin draining lymph nodes of IL-4 Tg mice was increased, consistent with the findings of >80% of skin-infiltrating T cells in Tg mice expressing CCR10. Chemotaxis transmigration assay demonstrated that CCL27 promotes a greater degree of migration of T cells in diseased Tg mice. Subcutaneous injection of neutralizing anti-CCL27 to IL-4 Tg mice with early skin lesions resulted in reduced clinical progression of inflammation, accompanied with decreased T cell and mast cell infiltration in the skin, and down-regulation of inflammatory cytokines. In conclusion, CCL27 and CCR10 interaction is important for the development of skin inflammation in our AD model.
Chen
Lin
L
Department of Dermatology, University of Illinois at Chicago, College of Medicine, MC624, 808 South Wood Street, Room 376, 60612, USA.
Lin
Shao-xia
SX
Agha-Majzoub
Rania
R
Overbergh
Lutgart
L
Mathieu
Chantal
C
Chan
Lawrence S
LS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D054425:Chemokine CCL27; D019742:Chemokines, CC / Q000096:biosynthesis / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D053547:Keratin-14; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007633:Keratins / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D012867:Skin / Q000276:immunology; D015854:Up-Regulation
C515706:CCR10 protein, human; C119538:Ccl27a protein, mouse; C515707:Ccr10 protein, mouse; D054425:Chemokine CCL27; D019742:Chemokines, CC; C507540:KRT14 protein, human; D053547:Keratin-14; C507446:Krt14 protein, mouse; D054447:Receptors, CCR10; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007633:Keratins