Hyperresponsive TH2 cells with enhanced nuclear factor-κB activation induce atopic dermatitis–like skin lesions in Nishiki-nezumi Cinnamon/Nagoya mice - 20/08/11
Reprint requests: Toshinori Nakayama, MD, Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 Japan.Chiba and Osaka, Japan
Abstract |
Background |
Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice raised in nonair-controlled conventional circumstances spontaneously develop atopic dermatitis-like skin lesions; however, the underlying mechanisms remain unclear.
Objective |
We wanted to identify the critical intracellular signaling molecules in T cells that induce atopic dermatitis-like skin legions in NC/Nga mice.
Methods |
We examined the levels of signal transduction and cytokine production in T cells, particularly those in atopic dermatitis-like lesions induced by the topical injection of mite antigens in NC/Nga mice under specific pathogen-free conditions.
Results |
In NC/Nga mice maintained under specific pathogen-free conditions, the capability of TH1/TH2 and T cytotoxic 1/T cytotoxic 2 (Tc1/Tc2) cell differentiation increased significantly. T-cell antigen receptor–mediated activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase cascade and nuclear factor-κB (NF-κB) signaling were enhanced in NC/Nga T cells. The expression of TH2 cytokines (IL-4, IL-13, and IL-5) and that of GATA-binding protein 3 (GATA3), avian musculoaponeurotic fibrosarcoma (c-Maf), NF-κB, and activator protein 1 (AP1) selectively increased in draining lymph node T cells of NC/Nga mice. Moreover, the cell transfer of inhibitory NF-κB mutant-infected TH2 cells reduced ear thickness in the mite antigen-induced skin lesion of NC/Nga mice.
Conclusion |
Hyperresponsive TH2 cells with an enhanced activity of NF-κB and AP1 play a crucial role in the pathogenesis of atopic dermatitis-like skin lesions in NC/Nga mice.
Clinical implications |
These results indicate potential therapeutic usefulness of developing selective inhibitors for NF-κB in the treatment of human atopic dermatitis.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, NC/Nga mouse, NF-κB, AP1, ERK/MAPK cascade, TH2
Abbreviations used : AD, DL, Dp, EMSA, ERK, IκB, IL-2R, IL-4R, MAPK, NC/Nga, NFAT, NF-κB, SPF, STAT, Tc, TCR
Plan
| Supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (Japan; Grants-in-Aid for Scientific Research in Priority Areas #17016010 and #17047007, Scientific Research B #17390139, Scientific Research C #18590466, Grant-in-Aid for Young Scientists #17790318, and Special Coordination Funds for Promoting Science and Technology), the Ministry of Health, Labor and Welfare (Japan), the Japan Health Science Foundation, the Kanae Foundation, the Uehara Memorial Foundation, and the Mochida Foundation. Disclosure of potential conflict of interest: The authors have received grant support from the Japanese government and foundations. |
Vol 118 - N° 3
P. 725-733 - septembre 2006 Retour au numéro
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