Signal Transducer and Activator of Transcription 6 Is Essential in the Induction of Contact Hypersensitivity

doi:10.1084/jem.191.6.995

Published online 20 March 2000.

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© The Rockefeller University Press, 0022-1007/2000/3/995/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 6, March 20, 2000 995-1004

Original Article

Signal Transducer and Activator of Transcription 6 Is Essential in the Induction of Contact Hypersensitivity

Hiroo Yokozeki^a, Mehran Ghoreishi^a, Shinsuke Takagawa^a, Kaoru Takayama^a, Takahiro Satoh^a, Ichiro Katayama^b, Kiyoshi Takeda^c, Shizuo Akira^c, and Kiyoshi Nishioka^a
^a Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
^b Department of Dermatology, School of Medicine, Nagasaki University, Nagasaki 852-8102, Japan
^c Department of Host Defense, Research Institute for Microbial Disease, Osaka University, Shuita, Osaka 565-0871, Japan

Correspondence to: Hiroo Yokozeki, Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Yushi-ma-1-chome, 5-45, Bunkyo-ku, Tokyo 113-8519, Japan. Tel:81-3-5803-5286 Fax:81-3-5803-0143 E-mail:3064.derm{at}med.tmd.ac.jp.

Released online: 20 March 2000

Contact hypersensitivity (CHS) is thought to be mainly associatedwith the activation of T helper type 1 (Th1) cells. However,there is also evidence that Th2 cells or Th2 cytokines playa role in the development of CHS. To analyze the functionalcontribution of Th2 cytokines interleukin (IL)-4 and IL-13,signal transducer and activator of transcription 6 (STAT6)-deficient(STAT6^-/-) and wild-type (wt) control C57BL/6 mice were contactsensitized with 5% 2,4,6-trinitrochlorobenzene (TNCB), 0.5%2,4-dinitrofluorobenzene, or 5% 4-ethoxyl methylene-2-phenyl-2-oxazolin-5-one,and any skin reactions were examined. Ear swelling was significantlyreduced with a delayed peak response in STAT6^-/- mice comparedwith wt mice.

A histological analysis revealed that the infiltration of botheosinophils and neutrophils in the skin challenged after 24h in STAT6^-/- mice decreased substantially compared with thatin wt mice. The expression of Th2 cytokines (IL-4, IL-5) inTNCB-challenged skin tissues and the supernatants from T cellsstimulated by 2,4,6-trinitrobenzene sulfonate–modifiedspleen cells, as well as the immunoglobulin (Ig)E and IgG1 responseafter challenge, were also profoundly reduced in STAT6^-/- mice,whereas the expression of interferon ${gamma}$ was the same in STAT6^-/-and wt mice after challenge. Furthermore, adoptive transferexperiments revealed that STAT6^-/- mice induced CHS after injectionof lymph node cells obtained from sensitized wt mice. Our datasuggest that the STAT6 signal plays a critical role in the inductionphase of CHS.

Key Words: signal transducer and activator of transcription factor 6, contacthypersensitivity, Th2, IL-4, IL-13

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