Hapten-induced contact hypersensitivity is enhanced in Tyk2-deficient mice.
BACKGROUND
Previous studies have shown that Tyk2, a member of the Janus family of protein tyrosine kinases, which are activated by a variety of cytokines, plays a crucial role in interleukin (IL)-12-mediated T-cell functions such as IFN-gamma production. On the other hand, hapten-induced contact hypersensitivity (CHS) is mediated by IFN-gamma producing CD8+ T cells and regulated by CD4+ T cells.


OBJECTIVE
This study hypothesized that the CHS response might be reduced in Tyk2-deficient mice because of a lack of IFN-gamma production from CD4+ and CD8+ T cells.


METHODS
The CHS reaction was evoked in wild-type and Tyk2-deficient mice and the ears of the mice were examined to measure for several cytokines.


RESULTS
Ear swelling during CHS was significantly enhanced in Tyk2-deficient mice compared with the controls. IL-12 and IFN-gamma levels at the reaction sites in Tyk2-deficient mice were significantly lower than in the controls, whereas IL-2 and IL-4 levels were elevated. Furthermore, STAT3- and STAT4-phosphorylation in the draining lymph node cells of Tyk2-deficient mice decreased.


CONCLUSIONS
These results suggest that the lack of Tyk2-mediated signal transduction enhances a compensative pathway during CHS.
Hosogi
Miwa
M
Biochemistry Laboratory, Pias Corporation, 1-3-1 Murotani, Nishi-ku, Kobe 651-2241, Japan. miwahoso@kuhp.kyoto-u.ac.jp
Tonogaito
Hiroshi
H
Aioi
Akihiro
A
Hamada
Kazuhiko
K
Shimoda
Kazuya
K
Muromoto
Ryuta
R
Matsuda
Tadashi
T
Miyachi
Yoshiki
Y
D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003877:Dermatitis, Contact / Q000201:enzymology*; D006241:Haptens / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D053634:TYK2 Kinase; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; D006241:Haptens; D007376:Interleukin-2; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse