A protease-activated pathway underlying Th cell type 2 activation and allergic lung disease.
The respiratory allergens that induce experimental Th cell type 2-dependent allergic lung inflammation may be grouped into two functional classes. One class of allergens, in this study termed type I, requires priming with adjuvants remote from the lung to overcome airway tolerogenic mechanisms that ordinarily preclude allergic responses to inhaled Ags. In contrast, the other, or type II, allergen class requires neither remote priming nor additional adjuvants to overcome airway tolerance and elicit robust allergic lung disease. In this study, we show in an experimental model that diverse type II allergens share in common proteolytic activity that is both necessary and sufficient for overcoming airway tolerance and induction of pulmonary allergic disease. Inactivated protease and protease-free Ag fragments showed no allergenic potency, demonstrating that only active protease acting on endogenous substrates was essential. Furthermore, induction of airway tolerance could be aborted and allergic lung disease established by simply adding purified protease to a type I allergen. Thus, exogenous proteases are common to type II allergens and may be generally required to overcome the innate resistance of the airway to Th cell type 2 activation and allergic inflammation, raising concern for their potential contribution to diseases such as asthma.
Kheradmand
Farrah
F
Biology of Inflammation Center, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.
Kiss
Attila
A
Xu
Jie
J
Lee
Seung-Hyo
SH
Kolattukudy
Pappachan E
PE
Corry
David B
DB
D000485:Allergens / Q000008:administration & dosage / Q000145:classification / Q000276:immunology*; D031164:Ambrosia / Q000201:enzymology / Q000276:immunology; D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis; D000946:Antigens, Fungal / Q000008:administration & dosage / Q000276:immunology; D001232:Aspergillus fumigatus / Q000201:enzymology / Q000276:immunology; D001236:Aspergillus oryzae / Q000201:enzymology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011058:Pollen / Q000201:enzymology / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D012697:Serine Endopeptidases / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*
D000485:Allergens; D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin; D012697:Serine Endopeptidases