Localization of intestinal intraepithelial T lymphocytes involves regulation of alphaEbeta7 expression by transforming growth factor-beta.
Induction of alphaEbeta7 expression on T cells by transforming growth factor (TGF)-beta is thought to be important for intestinal intraepithelial T lymphocyte (IEL) entry into the epithelial compartment. However, there has been no in vivo evidence that up-regulation of alphaEbeta7 expression on T cells by TGF-beta is critical for the selective localization of intestinal IEL in the epithelial area. We have recently established transgenic mice expressing Smad7 under the control of a distal lck promoter where TGF-beta/Smad signaling is specifically blocked in mature T cells. Here we showed that TGF-beta-mediated up-regulation of alphaEbeta7 was impaired on T cells isolated from the Smad7 transgenic mice associated with reduced numbers of intestinal IEL when compared with that in wild-type littermates. These results indicated that failure to induce alphaEbeta7 on T cells by TGF-beta resulted in reduced numbers of intestinal IEL, suggesting the importance of alphaEbeta7 expression by TGF-beta in selective localization of intestinal IEL.
Suzuki
Ryuyo
R
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Nakao
Atsuhito
A
Kanamaru
Yutaka
Y
Okumura
Ko
K
Ogawa
Hideoki
H
Ra
Chisei
C
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D016023:Integrins / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000494:pharmacology; D011994:Recombinant Proteins; D051906:Smad7 Protein; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D016023:Integrins; D011994:Recombinant Proteins; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C070709:integrin alphaEbeta7; D010047:Ovalbumin