Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes

Evans  HG; Suddason  T; Jackson  ITaams  LSLord  GM

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Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes

机译：Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes

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Recently, a new lineage of CD4(+) T cells has been described in the mouse that specifically secretes IL-17 T helper(Th) 17. This discovery has led to a revision of the hypothesis that many autoimmune diseases are predominantly a Th1 phenomenon and may instead be critically dependent on the presence of Th17 cells. Murine Th17 cells differentiate from naive T cell precursors in the presence of TGF-beta and IL-6 or IL-21. However, given their putative importance in human autoimmunity, very little is known about the pathways that control the expression of IL-17 in humans. Here we show that the factors that determine the expression of IL-17 in human CD4+ T cells are completely different from mice. IL-6 and IL-21 were unable to induce IL-17 expression in either naive or effector T cells, and TGF-beta actually inhibited IL-17 expression. The expression of IL-17 was maximally induced from precommitted precursors present in human peripheral blood by cell-cell contact with Toll-like receptor-activated monocytes in the context of T cell receptor ligation. Furthermore, unlike IFN-gamma, IL-17 expression was not suppressed by the presence of FOXP3(+) regulatory CD4+ T cells. Taken together, these data indicate that human and mouse Th17 cells have important biological differences that may be of critical importance in the development of therapeutic interventions in diseases characterized by aberrant T cell polarization.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2007年第43期|17034-17039|共6页
作者
Evans HG; Suddason T; Jackson ITaams LSLord GM;
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作者单位

Kings Coll London, Dept Immunobiol, London SE1 9RT, England;

Kings Coll London, Dept Nephrol & Transplantat, London SE1 9RT, England;

Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 USAGuys & St Thomas Hosp, Natl Inst Hlth Res Biomed Res Ctr, London SE1 9RT, England;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
autoimmunity; IL-17; T lymphocytes; TRANSCRIPTION FACTOR GATA-3; CYTOKINE GENE-EXPRESSION; GROWTH-FACTOR-BETA; HUMAN TH17 CELLS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; TGF-BETA; PERIPHERAL-BLOOD; SYNOVIAL-FLUID; EFFECTOR-CELLS;

Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes

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