ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses
Mast cells (MCs) are sentinel cells which represent an important part of the first line of defense of the immune system. MCs highly express receptors for danger-associated molecular patterns (DAMPs) such as the IL-33R and P2X7, making MCs to potentially effective sensors for IL-33 and adenosine-trip...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/23/2696 |
| _version_ | 1797400343759290368 |
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| author | Johanna Seifert Claudia Küchler Sebastian Drube |
| author_facet | Johanna Seifert Claudia Küchler Sebastian Drube |
| author_sort | Johanna Seifert |
| collection | DOAJ |
| description | Mast cells (MCs) are sentinel cells which represent an important part of the first line of defense of the immune system. MCs highly express receptors for danger-associated molecular patterns (DAMPs) such as the IL-33R and P2X7, making MCs to potentially effective sensors for IL-33 and adenosine-triphosphate (ATP), two alarmins which are released upon necrosis-induced cell damage in peripheral tissues. Besides receptors for alarmins, MCs also express the stem cell factor (SCF) receptor c-Kit, which typically mediates MC differentiation, proliferation and survival. By using bone marrow-derived MCs (BMMCs), ELISA and flow cytometry experiments, as well as p65/RelA and NFAT reporter MCs, we aimed to investigate the influence of SCF on alarmin-induced signaling pathways and the resulting cytokine production and degranulation. We found that the presence of SCF boosted the cytokine production but not degranulation in MCs which simultaneously sense ATP and IL-33 (ATP/IL-33 co-sensing). Therefore, we conclude that SCF maintains the functionality of MCs in peripheral tissues to ensure appropriate MC reactions upon cell damage, induced by pathogens or allergens. |
| first_indexed | 2024-03-09T01:54:10Z |
| format | Article |
| id | doaj.art-b9f6a252be0c4d2e8443c119d58d2cac |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T01:54:10Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b9f6a252be0c4d2e8443c119d58d2cac2023-12-08T15:13:05ZengMDPI AGCells2073-44092023-11-011223269610.3390/cells12232696ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine ResponsesJohanna Seifert0Claudia Küchler1Sebastian Drube2Institut für Immunologie, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Leutragraben 3, 07743 Jena, GermanyInstitut für Immunologie, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Leutragraben 3, 07743 Jena, GermanyInstitut für Immunologie, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Leutragraben 3, 07743 Jena, GermanyMast cells (MCs) are sentinel cells which represent an important part of the first line of defense of the immune system. MCs highly express receptors for danger-associated molecular patterns (DAMPs) such as the IL-33R and P2X7, making MCs to potentially effective sensors for IL-33 and adenosine-triphosphate (ATP), two alarmins which are released upon necrosis-induced cell damage in peripheral tissues. Besides receptors for alarmins, MCs also express the stem cell factor (SCF) receptor c-Kit, which typically mediates MC differentiation, proliferation and survival. By using bone marrow-derived MCs (BMMCs), ELISA and flow cytometry experiments, as well as p65/RelA and NFAT reporter MCs, we aimed to investigate the influence of SCF on alarmin-induced signaling pathways and the resulting cytokine production and degranulation. We found that the presence of SCF boosted the cytokine production but not degranulation in MCs which simultaneously sense ATP and IL-33 (ATP/IL-33 co-sensing). Therefore, we conclude that SCF maintains the functionality of MCs in peripheral tissues to ensure appropriate MC reactions upon cell damage, induced by pathogens or allergens.https://www.mdpi.com/2073-4409/12/23/2696mast cellsATP/IL-33 co-sensingstem cell factor (SCF)p65/RelANFAT |
| spellingShingle | Johanna Seifert Claudia Küchler Sebastian Drube ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses Cells mast cells ATP/IL-33 co-sensing stem cell factor (SCF) p65/RelA NFAT |
| title | ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses |
| title_full | ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses |
| title_fullStr | ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses |
| title_full_unstemmed | ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses |
| title_short | ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses |
| title_sort | atp il 33 co sensing by mast cells mcs requires activated c kit to ensure effective cytokine responses |
| topic | mast cells ATP/IL-33 co-sensing stem cell factor (SCF) p65/RelA NFAT |
| url | https://www.mdpi.com/2073-4409/12/23/2696 |
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