Amelioration of ovalbumin-induced allergic airway disease following Der p 1 peptide immunotherapy is not associated with induction of IL-35.
In the present study, we show therapeutic amelioration of established ovalbumin (OVA)-induced allergic airway disease following house dust mite (HDM) peptide therapy. Mice were sensitized and challenged with OVA and HDM protein extract (Dermatophagoides species) to induce dual allergen sensitization and allergic airway disease. Treatment of allergic mice with peptides derived from the major allergen Der p 1 suppressed OVA-induced airway hyperresponsiveness, tissue eosinophilia, and goblet cell hyperplasia upon rechallenge with allergen. Peptide treatment also suppressed OVA-specific T-cell proliferation. Resolution of airway pathophysiology was associated with a reduction in recruitment, proliferation, and effector function of T(H)2 cells and decreased interleukin (IL)-17⁺ T cells. Furthermore, peptide immunotherapy induced the regulatory cytokine IL-10 and increased the proportion of Fox p3⁺ cells among those expressing IL-10. Tolerance to OVA was not associated with increased IL-35. In conclusion, our results provide in vivo evidence for the creation of a tolerogenic environment following HDM peptide immunotherapy, leading to the therapeutic amelioration of established OVA-induced allergic airway disease.
Divisions of Respirology and Clinical Immunology and Allergy, Department of Medicine, McMaster Immunology Research Centre, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
D M
DM
Moldaver
Divisions of Respirology and Clinical Immunology and Allergy, Department of Medicine, McMaster Immunology Research Centre, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
M S
MS
Bharhani
Divisions of Respirology and Clinical Immunology and Allergy, Department of Medicine, McMaster Immunology Research Centre, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
J N
JN
Wattie
Divisions of Respirology and Clinical Immunology and Allergy, Department of Medicine, McMaster Immunology Research Centre, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
R
R
Ellis
Divisions of Respirology and Clinical Immunology and Allergy, Department of Medicine, McMaster Immunology Research Centre, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
H
H
Neighbour
Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London and MRC/Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
C M
CM
Lloyd
Divisions of Respirology and Clinical Immunology and Allergy, Department of Medicine, McMaster Immunology Research Centre, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
M D
MD
Inman
Divisions of Respirology and Clinical Immunology and Allergy, Department of Medicine, McMaster Immunology Research Centre, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
M
M
Larché
D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology*; D060829:Arthropod Proteins / Q000008:administration & dosage / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000276:immunology*; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010047:Ovalbumin / Q000009:adverse effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D015848:Interleukin-5; D007378:Interleukins; D010446:Peptide Fragments; C569375:interleukin-35, mouse; D016753:Interleukin-10; D010047:Ovalbumin; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1