Regulation of T helper type 2 cell differentiation by murine Schnurri-2.
Schnurri (Shn) is a large zinc finger protein implicated in cell growth, signal transduction, and lymphocyte development. Vertebrates possess at least three Shn orthologues (Shn-1, Shn-2, and Shn-3), which appear to act within the bone morphogenetic protein, transforming growth factor beta, and activin signaling pathways. However, the physiological functions of the Shn proteins remain largely unknown. In Shn-2-deficient mice, mature peripheral T cells exhibited normal anti-T cell receptor-induced proliferation, although there was dramatic enhancement in the differentiation into T helper type (Th)2 cells and a marginal effect on Th1 cell differentiation. Shn-2-deficient developing Th2 cells showed constitutive activation of nuclear factor kappaB (NF-kappaB) and enhanced GATA3 induction. Shn-2 was able to compete with p50 NF-kappaB for binding to a consensus NF-kappaB motif and inhibit NF-kappaB-driven promoter activity. Thus, Shn-2 plays a crucial role in the control of Th2 cell differentiation by regulating NF-kappaB function.
Kimura
Motoko Y
MY
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Hosokawa
Hiroyuki
H
Yamashita
Masakatsu
M
Hasegawa
Akihiro
A
Iwamura
Chiaki
C
Watarai
Hiroshi
H
Taniguchi
Masaru
M
Takagi
Tsuyoshi
T
Ishii
Shunsuke
S
Nakayama
Toshinori
T
D000818:Animals; D000911:Antibodies, Monoclonal; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; C490430:Hivep2 protein, mouse; D016328:NF-kappa B; D020033:Protein Isoforms; D011948:Receptors, Antigen, T-Cell; D015534:Trans-Activators