Stat6-independent tissue inflammation occurs selectively on the ocular surface and perioral skin of IkappaBzeta-/- mice.
OBJECTIVE
IkappaBzeta(-/-) mice have been reported to be affected by allergic dermatitis. This study was conducted to analyze the pathophysiological role of IkappaBzeta and to address the functional relevance of Th2-mediated immune responses in the development of ocular surface inflammation and dermatitis by IkappaBzeta(-/-) mice.


METHODS
BALB/c background IkappaBzeta(-/-) mice were established without individual differences; IkappaBzeta/Stat6 double-knockout (WKO) mice unable to produce Th2 cytokine were created; and microscopic-, histologic-, and immunochemical studies were performed. In IkappaBzeta(-/-) mice the serum IgE levels were examined by ELISA, and quantitative PCR was used to study the gene expression of IFN-gamma, IL4, IL10, TNFalpha, IL6, IL17alpha, and CCL11 in eyelid tissue.


RESULTS
IkappaBzeta(-/-) mice exhibited a severe inflammatory phenotype on the ocular surface and perioral skin. The inflammatory infiltrates in the perioral skin consisted primarily of CD4(+) and CD8(+) cells; CD4(+) and CD45R/B220(+) cells were mainly detected in the conjunctiva. In eyelid and perioral skin tissue, the expression of IL-17alpha and of Th1 and Th2 cytokines, but not of CCL11, was augmented. IkappaBzeta(-/-) and IkappaBzeta(+/-) mice did not differ significantly in their serum total IgE levels before, 0 to 4 weeks, and 5 to 9 weeks after disease onset. IkappaBzeta/Stat6 WKO mice showed the same or slightly more severe inflammation than did IkappaBzeta(-/-) mice.


CONCLUSIONS
IgE and Stat6 are not responsible for the immune pathologic response leading to the development of ocular surface and perioral skin inflammation in IkappaBzeta(-/-) mice. IkappaBzeta(-/-) mice may be a suitable model for Stevens-Johnson syndrome, but not for atopic dermatitis.
Ueta
Mayumi
M
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. mueta@koto.kpu-m.ac.jp
Hamuro
Junji
J
Ueda
Eiichiro
E
Katoh
Norito
N
Yamamoto
Masahiro
M
Takeda
Kiyoshi
K
Akira
Shizuo
S
Kinoshita
Shigeru
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003228:Conjunctiva / Q000473:pathology; D003231:Conjunctivitis / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D019557:Dermatitis, Perioral / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D005838:Genotype; D020397:Goblet Cells / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D013262:Stevens-Johnson Syndrome / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; C485947:Nfkbiz protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D007073:Immunoglobulin E