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RESEARCH PRODUCT

Cutting Edge: Trans-Signaling via the Soluble IL-6R Abrogates the Induction of FoxP3 in Naive CD4+CD25− T Cells

Giovanni MonteleoneClemens NeufertMassimo FantiniChristoph BeckerJürgen SchellerMarkus F. NeurathStefan Rose-johnAlexei NikolaevSabine DominitzkiPeter R. Galle

subject

Regulatory T cellImmunologyMice Transgenicchemical and pharmacologic phenomenaMice SCIDBiologyT-Lymphocytes RegulatoryAutoimmune DiseasesSmad7 ProteinMiceInterleukin 21Immune systemTransforming Growth Factor betaImmunitymedicineAnimalsHumansImmunology and AllergyCytotoxic T cellIL-2 receptorInflammationMice Inbred BALB CInterleukin-6ZAP70FOXP3Forkhead Transcription FactorsColitisReceptors Interleukin-6Cell biologyDisease Models Animalmedicine.anatomical_structureGene Expression RegulationChronic DiseaseImmunologySignal Transduction

description

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.

yearjournalcountryeditionlanguage
2007-08-07The Journal of Immunology
https://doi.org/10.4049/jimmunol.179.4.2041