Janus-faced Acrolein prevents allergy but accelerates tumor growth by promoting immunoregulatory Foxp3+ cells: Mouse model for passive respiratory exposure.
Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal exposure to acrolein abrogated allergen-specific antibody and cytokine formation, and led to a relative accumulation of regulatory T cells in the lungs. Only the acrolein-treated mice were protected from bronchial hyperreactivity as well as from anaphylactic reactions upon challenge with the specific allergen. Moreover, grafted D2F2 tumor cells grew faster and intratumoral Foxp3+ cell accumulation was observed in these mice compared to sham-treated controls. Results from reporter cell lines suggested that acrolein acts via the aryl-hydrocarbon receptor which could be inhibited by resveratrol and 3'-methoxy-4'-nitroflavone Acrolein- stimulation of human PBMCs increased Foxp3+ expression by T cells which could be antagonized by resveratrol. Our mouse and human data thus revealed that acrolein exerts systemic immunosuppression by promoting Foxp3+ regulatory cells. This provides a novel explanation why smokers have a lower allergy, but higher cancer risk.
Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Franziska
F
Roth-Walter
Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Cornelia
C
Bergmayr
Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Sarah
S
Meitz
Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Stefan
S
Buchleitner
Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Caroline
C
Stremnitzer
Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Judit
J
Fazekas
Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Anna
A
Moskovskich
Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Mario A
MA
Müller
Department of Anesthesiology, General Intensive Care and Pain Medicine, Medical University of Vienna, Austria.
Georg A
GA
Roth
Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Krisztina
K
Manzano-Szalai
Department of Cell Biology and Genetics, Palacky University, Olomouc, Czech Republic.
Zdenek
Z
Dvorak
Christian Doppler Laboratory for Immunomodulation, Medical University of Vienna, Vienna, Austria.
Alina
A
Neunkirchner
Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria.|Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Erika
E
Jensen-Jarolim
D000171:Acrolein / Q000494:pharmacology*; D000485:Allergens / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology* / Q000517:prevention & control*; D007155:Immunologic Factors / Q000494:pharmacology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
D000485:Allergens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007155:Immunologic Factors; D016328:NF-kappa B; D018336:Receptors, Aryl Hydrocarbon; D013267:Stilbenes; D000171:Acrolein; D000077185:Resveratrol