Signal transducer and activator of transcription 6 is essential in the induction of contact hypersensitivity.
Contact hypersensitivity (CHS) is thought to be mainly associated with the activation of T helper type 1 (Th1) cells. However, there is also evidence that Th2 cells or Th2 cytokines play a role in the development of CHS. To analyze the functional contribution 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 contact sensitized 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 significantly reduced with a delayed peak response in STAT6(-/)- mice compared with wt mice.A histological analysis revealed that the infiltration of both eosinophils and neutrophils in the skin challenged after 24 h in STAT6(-/)- mice decreased substantially compared with that in wt mice. The expression of Th2 cytokines (IL-4, IL-5) in TNCB-challenged skin tissues and the supernatants from T cells stimulated by 2,4,6-trinitrobenzene sulfonate-modified spleen cells, as well as the immunoglobulin (Ig)E and IgG1 response after 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 transfer experiments revealed that STAT6(-/)- mice induced CHS after injection of lymph node cells obtained from sensitized wt mice. Our data suggest that the STAT6 signal plays a critical role in the induction phase of CHS.
Yokozeki
H
H
Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan. 3064.derm@med.tmd.ac.jp
Ghoreishi
M
M
Takagawa
S
S
Takayama
K
K
Satoh
T
T
Katayama
I
I
Takeda
K
K
Akira
S
S
Nishioka
K
K
D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry; D002452:Cell Count; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007509:Irritants / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010080:Oxazoles / Q000276:immunology; D010853:Picryl Chloride / Q000276:immunology; D050800:STAT6 Transcription Factor; D012756:Sheep; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018800:Thy-1 Antigens / Q000096:biosynthesis; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C119678:4-ethoxymethylene-2-phenyl-2-oxazoline-5-one; D000954:Antigens, Surface; D016207:Cytokines; D007074:Immunoglobulin G; D007509:Irritants; D010080:Oxazoles; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D018800:Thy-1 Antigens; D015534:Trans-Activators; D007073:Immunoglobulin E; D004139:Dinitrofluorobenzene; D010853:Picryl Chloride