Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammation.
Adaptive Foxp3(+) regulatory T (Treg) cells develop during induction of mucosal tolerance and after immunization. Large numbers of Foxp3(+) T cells have been found in inflamed tissues. We investigated the role of adaptive Foxp3(+) Treg cells in mucosal tolerance and in chronic allergic lung inflammation. We used two strains of mice that are devoid of naturally occurring Treg cells; one is capable of generating adaptive Foxp3(+) Treg cells upon exposure to antigen, whereas the other is deficient in both naturally occurring and adaptive Foxp3(+) Treg cells. We found that adaptive Foxp3(+) Treg cells were essential for establishing mucosal tolerance and for suppressing IL-4 production and lymphoid neogenesis in chronic inflammation, whereas IL-5 production and eosinophilia could be controlled by Foxp3-independent, IFN-gamma-dependent mechanisms. Thus, whereas adaptive Foxp3(+) Treg cells regulate sensitization to allergens and the severity of chronic inflammation, IFN-gamma-producing cells can play a beneficial role in inflammatory conditions involving eosinophils.
Curotto de Lafaille
Maria A
MA
Program of Molecular Pathogenesis, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. curotto@saturn.med.nyu.edu
Kutchukhidze
Nino
N
Shen
Shiqian
S
Ding
Yi
Y
Yee
Herman
H
Lafaille
Juan J
JJ
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007249:Inflammation / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010047:Ovalbumin / Q000276:immunology; D016133:Polymerase Chain Reaction; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D010047:Ovalbumin