Chronic inflammatory diseases may develop when regulatory T cells (Tregs) fail to control the balance between tolerance and immunity. Alternatively, activated immune cells might prevent the induction or activation of Tregs in such diseases. In this study, we demonstrate that trans-signaling into T cells via the soluble IL-6 receptor completely abrogates the de novo induction of adaptive Tregs. Mechanistically, IL-6 trans-signaling augmented the expression of the TGF-β signaling inhibitor SMAD7. Consequently, SMAD7 overexpression in T cells using newly created transgenic mice rendered CD4+CD25 - T cells resistant to the induction of FoxP3. Finally, IL-6 trans-signaling inhibited Treg-mediated suppression in a murine model of colitis. In summary, IL-6 trans-signaling into T cells emerges as a key pathway for blockade of the development of adaptive Tregs and thus may play a pivotal role in shifting the balance between effector and regulatory T cell numbers in chronic inflammatory and autoimmune diseases. Copyright © 2007 by The American Association of Immunologists, Inc.

Dominitzki, S., Fantini, M.c., Neufert, C., Nikolaev, A., Galle, P.r., Scheller, J., et al. (2007). Cutting edge: Trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25- T cells. JOURNAL OF IMMUNOLOGY, 179(4), 2041-2045.

Cutting edge: Trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25- T cells

FANTINI, MASSIMO CLAUDIO;MONTELEONE, GIOVANNI;
2007-01-01

Abstract

Chronic inflammatory diseases may develop when regulatory T cells (Tregs) fail to control the balance between tolerance and immunity. Alternatively, activated immune cells might prevent the induction or activation of Tregs in such diseases. In this study, we demonstrate that trans-signaling into T cells via the soluble IL-6 receptor completely abrogates the de novo induction of adaptive Tregs. Mechanistically, IL-6 trans-signaling augmented the expression of the TGF-β signaling inhibitor SMAD7. Consequently, SMAD7 overexpression in T cells using newly created transgenic mice rendered CD4+CD25 - T cells resistant to the induction of FoxP3. Finally, IL-6 trans-signaling inhibited Treg-mediated suppression in a murine model of colitis. In summary, IL-6 trans-signaling into T cells emerges as a key pathway for blockade of the development of adaptive Tregs and thus may play a pivotal role in shifting the balance between effector and regulatory T cell numbers in chronic inflammatory and autoimmune diseases. Copyright © 2007 by The American Association of Immunologists, Inc.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/12 - GASTROENTEROLOGIA
English
interleukin 6 receptor; Smad7 protein; transcription factor FOXP3; transforming growth factor beta; forkhead transcription factor; Foxp3 protein, mouse; IL6 protein, human; interleukin 6; Smad7 protein, mouse; animal experiment; animal model; animal tissue; article; CD4+ CD25+ T lymphocyte; cell maturation; colitis; controlled study; flow cytometry; mouse; nonhuman; priority journal; protein expression; protein function; regulatory T lymphocyte; signal transduction; animal; autoimmune disease; Bagg albino mouse; biosynthesis; chronic disease; disease model; gene expression regulation; genetics; human; immunology; inflammation; metabolism; mouse mutant; pathology; transgenic mouse; Animals; Autoimmune Diseases; Chronic Disease; Colitis; Disease Models, Animal; Forkhead Transcription Factors; Gene Expression Regulation; Humans; Inflammation; Interleukin-6; Mice; Mice, Inbred BALB C; Mice, SCID; Mice, Transgenic; Receptors, Interleukin-6; Signal Transduction; Smad7 Protein; T-Lymphocytes, Regulatory; Transforming Growth Factor beta
PMID: 17675459
Dominitzki, S., Fantini, M.c., Neufert, C., Nikolaev, A., Galle, P.r., Scheller, J., et al. (2007). Cutting edge: Trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25- T cells. JOURNAL OF IMMUNOLOGY, 179(4), 2041-2045.
Dominitzki, S; Fantini, Mc; Neufert, C; Nikolaev, A; Galle, Pr; Scheller, J; Monteleone, G; Rose John, S; Neurath, Mf; Becker, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39358
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