title: Eotaxins and CCR3 interaction regulates the Th2 environment of cutaneous T-cell lymphoma.
abstract: CC chemokine receptor 3 (CCR3), the sole receptor for eotaxins, is expressed on eosinophils and T helper type 2 (Th2) cells. In Hodgkin's disease, eotaxin-1 secreted by fibroblasts collects Th2 cells and eosinophils within the tissue. Similarly, many Th2 cells infiltrate the lesional skin of cutaneous T-cell lymphoma (CTCL). In this study, we investigated the role of eotaxins in the development of the Th2 environment of CTCL. We revealed that fibroblasts from lesional skin of CTCL expressed higher amounts of eotaxin-3 messenger RNA (mRNA) compared with those from normal skin. Lesional skin of CTCL at advanced stages contained significantly higher levels of eotaxin-3 and CCR3 mRNA, compared with early stages of CTCL. IL-4 mRNA was expressed in some cases at advanced stages. Immunohistochemistry revealed that keratinocytes, endothelial cells, and dermal fibroblasts in lesional skin of CTCL showed a stronger expression of eotaxin-3 than did normal skin. CCR3(+) lymphocytes and IL-4 expression were observed in some cases of advanced CTCL. Furthermore, both serum eotaxin-3 and eotaxin-1 levels of CTCL patients at advanced stages were significantly higher than those of healthy individuals. The concentrations of these chemokines correlated with serum soluble IL-2 receptor levels. These results suggest that interaction of eotaxins and CCR3 regulates the Th2-dominant tumor environment, which is closely related to the development of CTCL.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyagaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugaya
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujita
authors.forename: Hanako
authors.initials: H
authors.lastname: Ohmatsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kakinuma
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tamaki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000097:blood; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012995:Solubility; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C515456:CCL11 protein, human; C120429:CCL26 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D000075906:Chemokine CCL26; D019742:Chemokines, CC; C508598:IL4 protein, human; D012333:RNA, Messenger; D054397:Receptors, CCR3; D015375:Receptors, Interleukin-2; D015847:Interleukin-4