Signaling pathways activated by a protease allergen in basophils
Allergic diseases represent a significant burden in industrialized countries, but why and how the immune system responds to allergens remain largely unknown. Because many clinically significant allergens have proteolytic activity, and many helminths express proteases that are necessary for their lif...
| Main Authors: | , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2014
|
| _version_ | 1797077513256566784 |
|---|---|
| author | Rosenstein, R Bezbradica, J Yu, S Medzhitov, R |
| author_facet | Rosenstein, R Bezbradica, J Yu, S Medzhitov, R |
| author_sort | Rosenstein, R |
| collection | OXFORD |
| description | Allergic diseases represent a significant burden in industrialized countries, but why and how the immune system responds to allergens remain largely unknown. Because many clinically significant allergens have proteolytic activity, and many helminths express proteases that are necessary for their life cycles, host mechanisms likely have evolved to detect the proteolytic activity of helminth proteases, which may be incidentally activated by protease allergens. A cysteine protease, papain, is a prototypic protease allergen that can directly activate basophils and mast cells, leading to the production of cytokines, including IL-4, characteristic of the type 2 immune response. The mechanism of papain’s immunogenic activity remains unknown. Here we have characterized the cellular response activated by papain in basophils. We find that papain-induced IL-4 production requires calcium flux and activation of PI3K and nuclear factor of activated T cells. Interestingly, papain-induced IL-4 production was dependent on the immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein Fc receptor γ-chain, even though the canonical ITAM signaling was not activated by papain. Collectively, these data characterize the downstream signaling pathway activated by a protease allergen in basophils. |
| first_indexed | 2024-03-07T00:19:08Z |
| format | Journal article |
| id | oxford-uuid:7be983d2-f039-4447-9dc7-49000b3c0dad |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:19:08Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:7be983d2-f039-4447-9dc7-49000b3c0dad2022-03-26T20:53:38ZSignaling pathways activated by a protease allergen in basophilsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7be983d2-f039-4447-9dc7-49000b3c0dadEnglishSymplectic Elements at OxfordNational Academy of Sciences2014Rosenstein, RBezbradica, JYu, SMedzhitov, RAllergic diseases represent a significant burden in industrialized countries, but why and how the immune system responds to allergens remain largely unknown. Because many clinically significant allergens have proteolytic activity, and many helminths express proteases that are necessary for their life cycles, host mechanisms likely have evolved to detect the proteolytic activity of helminth proteases, which may be incidentally activated by protease allergens. A cysteine protease, papain, is a prototypic protease allergen that can directly activate basophils and mast cells, leading to the production of cytokines, including IL-4, characteristic of the type 2 immune response. The mechanism of papain’s immunogenic activity remains unknown. Here we have characterized the cellular response activated by papain in basophils. We find that papain-induced IL-4 production requires calcium flux and activation of PI3K and nuclear factor of activated T cells. Interestingly, papain-induced IL-4 production was dependent on the immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein Fc receptor γ-chain, even though the canonical ITAM signaling was not activated by papain. Collectively, these data characterize the downstream signaling pathway activated by a protease allergen in basophils. |
| spellingShingle | Rosenstein, R Bezbradica, J Yu, S Medzhitov, R Signaling pathways activated by a protease allergen in basophils |
| title | Signaling pathways activated by a protease allergen in basophils |
| title_full | Signaling pathways activated by a protease allergen in basophils |
| title_fullStr | Signaling pathways activated by a protease allergen in basophils |
| title_full_unstemmed | Signaling pathways activated by a protease allergen in basophils |
| title_short | Signaling pathways activated by a protease allergen in basophils |
| title_sort | signaling pathways activated by a protease allergen in basophils |
| work_keys_str_mv | AT rosensteinr signalingpathwaysactivatedbyaproteaseallergeninbasophils AT bezbradicaj signalingpathwaysactivatedbyaproteaseallergeninbasophils AT yus signalingpathwaysactivatedbyaproteaseallergeninbasophils AT medzhitovr signalingpathwaysactivatedbyaproteaseallergeninbasophils |