Coexpression of TGF-beta1 and IL-10 enables regulatory T cells to completely suppress airway hyperreactivity.
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-beta1. Using mice with impaired TGF-beta signaling in T cells, we could demonstrate that TGF-beta 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-beta1 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.
Presser
Katrin
K
Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Schwinge
Dorothee
D
Wegmann
Michael
M
Huber
Samuel
S
Schmitt
Steffen
S
Quaas
Alexander
A
Maxeiner
Joachim H
JH
Finotto
Susetta
S
Lohse
Ansgar W
AW
Blessing
Manfred
M
Schramm
Christoph
C
D019264:Adoptive Transfer; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D053773:Transforming Growth Factor beta1; D016753:Interleukin-10