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前沿:肠道归巢功能受损的CD4+CD25+调节性T细胞可预防结肠炎。

Cutting edge: CD4+CD25+ regulatory T cells impaired for intestinal homing can prevent colitis.

作者信息

Denning Timothy L, Kim Gisen, Kronenberg Mitchell

机构信息

Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.

出版信息

J Immunol. 2005 Jun 15;174(12):7487-91. doi: 10.4049/jimmunol.174.12.7487.

Abstract

Transfer of CD4(+)CD45RB(high) T cells into RAG(-/-) mice causes colitis, which can be prevented by CD4(+)CD25(+) regulatory T cells (Treg). Colitis induction by CD4(+)CD45RB(high) T cells requires beta(7) integrin-dependent intestinal localization, but the importance of beta(7) integrins for Treg function is unknown. In this study, we show that beta(7)(-/-) Treg were effective in preventing colitis. Treg expanded in vivo to the same extent as CD4(+)CD45RB(high) T cells after transfer and they did not inhibit CD4(+)CD45RB(high) T cell expansion in lymphoid tissues, although they prevented the accumulation of Th1 effector cells in the intestine. beta(7)(-/-) Treg were significantly reduced in the large intestine, however, compared with wild-type Treg, and regulatory activity could not be recovered from the intestine of recipients of beta(7)(-/-) Treg. These data demonstrate that Treg can prevent colitis by inhibiting the accumulation of tissue-seeking effector cells and that Treg accumulation in the intestine is dispensable for colitis suppression.

摘要

将CD4(+)CD45RB(high) T细胞转移至RAG(-/-)小鼠体内会引发结肠炎,而CD4(+)CD25(+)调节性T细胞(Treg)可预防这种结肠炎。CD4(+)CD45RB(high) T细胞诱导结肠炎需要β(7)整合素依赖性肠道定位,但β(7)整合素对Treg功能的重要性尚不清楚。在本研究中,我们发现β(7)(-/-) Treg在预防结肠炎方面有效。转移后,Treg在体内的扩增程度与CD4(+)CD45RB(high) T细胞相同,并且它们不会抑制淋巴组织中CD4(+)CD45RB(high) T细胞的扩增,尽管它们可防止肠道中Th1效应细胞的积累。然而,与野生型Treg相比,β(7)(-/-) Treg在大肠中的数量显著减少,并且无法从接受β(7)(-/-) Treg的受体肠道中恢复调节活性。这些数据表明,Treg可通过抑制趋化至组织的效应细胞的积累来预防结肠炎,并且Treg在肠道中的积累对于抑制结肠炎并非必需。

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