Regulatory mechanisms of galectin-9 and eotaxin-3 synthesis in epidermal keratinocytes: possible involvement of galectin-9 in dermal eosinophilia of Th1-polarized skin inflammation.
BACKGROUND
Skin eosinophilia is a common feature of allergic skin diseases, but it is unclear how epidermal and dermal eosinophil infiltration is controlled. To investigate regulation of localization of eosinophils in skin, we examined the regulatory mechanisms of expression of eosinophil-specific chemoattractants in dermal fibroblasts and epidermal keratinocytes.


METHODS
We analyzed production of eotaxin, eotaxin-2, eotaxin-3 and galectin-9 by dermal fibroblasts and epidermal keratinocytes in response to several stimuli in vitro.


RESULTS
Dermal fibroblasts produced eotaxin and eotaxin-3 in response to stimulation by interleukin (IL)-4 and/or tumor necrosis factor-alpha. Similarly, IL-4 stimulated epidermal keratinocytes to secrete eotaxin-3. However, we did not detect eotaxin mRNA expression or protein secretion by keratinocytes stimulated in vitro. Interferon (IFN)-gamma induced galectin-9 expression on dermal fibroblasts. Conversely, expression of galectin-9 on epidermal keratinocytes was dose-dependently inhibited by IFN-gamma. The immunohistochemical assays revealed that dermal fibroblasts (but not epidermal keratinocytes) in the lesional skin of psoriasis vulgaris (a Th1-polarized disease) express significant levels of galectin-9.


CONCLUSIONS
Eotaxin-3 contributes to dermal and epidermal eosinophil infiltration in Th2-polarized skin inflammation in which IL-4 is produced. In contrast, IFN-gamma-dominated inflammation appears to mediate eosinophil extravasation into the dermis and eosinophil adhesion to dermal fibroblasts via galectin-9 in association with decreased chemoattractant activity of epidermal galectin-9. The present results reveal a novel mechanism of dermal eosinophilia in IFN-gamma-mediated skin inflammation, and reflect concerted chemoattractant production involving dermal and/or epidermal eosinophilia during changes in the local cytokine profile.
Igawa
K
K
Department of Dermatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Satoh
T
T
Hirashima
M
M
Yokozeki
H
H
D000818:Animals; D002478:Cells, Cultured; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000096:biosynthesis*; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics; D003872:Dermatitis / Q000473:pathology*; D004802:Eosinophilia / Q000473:pathology*; D000078404:Epidermal Cells; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D037161:Galectins / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology
C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D002630:Chemotactic Factors; D037161:Galectins; C105032:LGALS9 protein, human; D015847:Interleukin-4; D007371:Interferon-gamma