Differential production of Th1- and Th2-type chemokines by mouse Langerhans cells and splenic dendritic cells.
Some chemokines specifically attract T helper 1 (Th1) cells, whereas others attract T helper 2 (Th2) cells. In this study, we investigated the capacity of Langerhans cells (LC) to produce Th1- and Th2-type chemokines in comparison with that of splenic CD11c(+) dendritic cells (DC). We prepared highly purified (>95%) LC from BALB/c mouse skin using the panning method. With regard to Th1-type chemokines, exogenous stimulus, such as interferon-gamma (IFN-gamma), lipopolysaccharide, or polyinosinic-polycytidylic acid, was mandatory for the production of substantial amounts of CXCL10, CXCL9, and CXCL11 both in LC and splenic DC. LC, as a whole, exhibited low ability to produce Th1-type chemokines in comparison with splenic DC. As for Th2-type chemokines, LC, but not splenic DC, produced high levels of CCL22 and CCL17 constitutively during culture even without exogenous stimuli. The production of Th2-type chemokines was regulated in a complicated manner. In particular, interleukin-4 upregulated, and IFN-gamma downregulated both CCL22 and CCL17 production by LC. Of note, LC produced much more amounts of Th2-type chemokines than splenic DC under any conditions tested. Finally, Th1- and Th2-type chemokines produced by LC were shown to be functional using chemokine receptor-transfected-2B4 T cells. The high production of CC chemokine receptor 4 ligands by LC in the absence of IFN-gamma may be an important character discriminating LC from other DC.
Fujita
Hideki
H
Department of Dermatology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan.
Asahina
Akihiko
A
Sugaya
Makoto
M
Nakamura
Koichiro
K
Gao
Ping
P
Fujiwara
Hiromi
H
Tamaki
Kunihiko
K
D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D018925:Chemokines / Q000235:genetics*; D019742:Chemokines, CC / Q000235:genetics; D019743:Chemokines, CXC / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D039521:CD11c Antigen; C499538:Ccl17 protein, mouse; C515483:Ccl22 protein, mouse; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; C515203:Cxcl11 protein, mouse; C485969:Cxcl9 protein, mouse; D012333:RNA, Messenger; D007371:Interferon-gamma