RESUMO
IgE induced by type 2 immune responses in atopic dermatitis is implicated in the progression of atopic dermatitis to other allergic diseases, including food allergies, allergic rhinitis, and asthma. However, the keratinocyte-derived signals that promote IgE and ensuing allergic diseases remain unclear. Herein, in a mouse model of atopic dermatitis-like skin inflammation induced by epicutaneous Staphylococcus aureus exposure, keratinocyte release of IL36α along with IL-4 triggered B cell IgE class-switching, plasma cell differentiation, and increased serum IgE levels-all of which were abrogated in IL-36R-deficient mice or anti-IL36R-blocking antibody-treated mice. Moreover, skin allergen sensitization during S. aureus epicutaneous exposure-induced IL-36 responses was required for the development of allergen-specific lung inflammation. In translating these findings, elevated IL36 cytokines in human atopic dermatitis skin and in IL36 receptor antagonist-deficiency patients coincided with increased serum IgE levels. Collectively, keratinocyte-initiated IL36 responses represent a key mechanism and potential therapeutic target against allergic diseases.
Assuntos
Dermatite Atópica/imunologia , Imunoglobulina E/imunologia , Interleucina-1/imunologia , Queratinócitos/imunologia , Plasmócitos/imunologia , Staphylococcus aureus/imunologia , Animais , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Dermatite Atópica/genética , Dermatite Atópica/microbiologia , Humanos , Switching de Imunoglobulina , Imunoglobulina E/genética , Interleucina-1/genética , Interleucina-4/genética , Interleucina-4/imunologia , Queratinócitos/microbiologia , Camundongos , Camundongos Knockout , Plasmócitos/patologiaRESUMO
An IgG mouse monoclonal antibody (10F05) against polyethylene glycol has been generated. The antibody reacts with PEG regardless of the linker used for PEG attachment, and is able to recognize a PEGylated peptide in plasma at concentrations as low as 3 pg/mL. The antibody is readily purified in substantial quantities. The PEG IgG will find significant utility in the sensitive detection of PEG derivitives during the pharmacokinetic characterization of PEGylated compounds.