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RESEARCH PRODUCT
Coexpression of TGF-β1 and IL-10 Enables Regulatory T Cells to Completely Suppress Airway Hyperreactivity
Alexander QuaasManfred BlessingChristoph SchrammAnsgar W. LohseDorothee SchwingeSusetta FinottoMichael WegmannJoachim MaxeinerKatrin PresserSteffen SchmittSamuel Hubersubject
Adoptive cell transferTransgeneImmunologyGene ExpressionMice Transgenicchemical and pharmacologic phenomenaInflammationT-Lymphocytes RegulatoryTransforming Growth Factor beta1MiceRespiratory HypersensitivitymedicineAnimalsImmunology and AllergyAsthmaInflammationbusiness.industryEffectorhemic and immune systemsrespiratory systemmedicine.diseaseAdoptive TransferAirway hyperreactivityInterleukin-10respiratory tract diseasesDisease Models AnimalInterleukin 10Immunologymedicine.symptombusinessSignal TransductionTransforming growth factordescription
Abstract In allergic airway disease, Treg may play an important role in the modulation of airway hyperreactivity (AHR) and inflammation. We therefore investigated the therapeutic potential of Treg in an Ag-dependent murine asthma model. We here describe that AHR can be completely suppressed by adoptive transfer of Treg overexpressing active TGF-β1. Using mice with impaired TGF-β signaling in T cells, we could demonstrate that TGF-β signaling in recipient effector T cells or transferred Treg themselves is not required for the protective effects on AHR. However, the expression of IL-10 by Treg was found to be essential for the suppression of AHR, since Treg overexpressing active TGF-β1 but deficient in IL-10 lacked protective effects. Airway inflammation could not be significantly suppressed by wild-type or transgenic Treg. In conclusion, modulation of cytokine expression by Treg may have therapeutic potential for the treatment of AHR in asthma. The mechanisms of the effects of Treg on airway inflammation require further clarification.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-12-01 | The Journal of Immunology |