UVB irradiation of normal human skin favors the development of type-2 T-cells in vivo and in primary dermal cell cultures.
To determine the effect of UVB exposure on the balance of type-1 or type-2 T-cells in skin, we examined the expression of key markers interferon (IFN)-gamma and interleukin (IL)-4 in cryostat sections. IFN-gamma mRNA was clearly detectable in nonirradiated control skin, and IFN-gamma protein was found in 2% of the dermal CD3pos T-cells, whereas IL-4 mRNA was hardly detectable, and no IL-4 protein was found. In contrast, IL-4 mRNA expression increased upon irradiation, and IL-4 was found in 2% of the T-cells at day 2 after UVB-exposure. Concomitantly, IFN-gamma mRNA expression decreased, and IFN-gamma protein became absent. We also analyzed T-cells present in primary dermal cell cultures, which were used as an in vitro equivalent of the in vivo situation. As compared with T-cells from control skin, T-cells in dermal cell cultures from UVB-exposed skin displayed an increased IL-4 and decreased IFN-gamma expression. No such skewing occurred when the T-cells from irradiated skin were cloned in the absence of a dermal microenvironment. Except for an occasional positive T-cell, type-1-associated cell-surface markers (CCR5, CXCR3) or type-2 markers (CCR3, CD30, CRTH2) were undetectable in situ. But these markers were expressed on cultured dermal T-cells from UVB-exposed and control skin at a comparable level, but did not correlate with the IFN-gamma and IL-4 production. Altogether, UVB-induced changes of the dermal microenvironment favor the development of type-2 T-cells.
Di Nuzzo
Sergio
S
Department of Dermatology, Academic Medical Center, University of Amsterdam, The Netherlands.
Sylva-Steenland
Regien M R
RM
Koomen
Cornelis W
CW
Nakagawa
Satoshi
S
van Breemen
Marielle
M
de Rie
Menno A
MA
Das
Pranab K
PK
Bos
Jan D
JD
Teunissen
Marcel B M
MB
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D014466:Ultraviolet Rays
D017931:DNA Primers; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma