Dectin-1 stimulation induces suppressor of cytokine signaling 1, thereby modulating TLR signaling and T cell responses
Suppressor of cytokine signaling (SOCS) proteins serve as negative regulators of cytokine receptor signaling. However, SOCS proteins are not only induced via the JAK/STAT pathway, but are also transcribed on triggering of pattern recognition receptors such as TLRs. We now show that SOCS1 can also be...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
30 April 2012
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| In: |
The journal of immunology
Year: 2012, Volume: 188, Issue: 11, Pages: 5644-5654 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.1103068 |
| Online Access: | Verlag, Volltext: https://doi.org/10.4049/jimmunol.1103068 Verlag, Volltext: http://www.jimmunol.org/content/188/11/5644 
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| Author Notes: | Mariel E. Eberle and Alexander H. Dalpke |
| Summary: | Suppressor of cytokine signaling (SOCS) proteins serve as negative regulators of cytokine receptor signaling. However, SOCS proteins are not only induced via the JAK/STAT pathway, but are also transcribed on triggering of pattern recognition receptors such as TLRs. We now show that SOCS1 can also be induced by the non-TLR pattern recognition receptor Dectin-1 in murine bone marrow-derived dendritic cells and macrophages (BMMs). The C-type lectin Dectin-1 binds to yeasts and signals either in an autonomous manner or can be triggered in combination with TLRs. In our study, SOCS1 was expressed independently of any TLR engagement as a direct target gene of the Dectin-1 ligand Zymosan. Induction of SOCS1 was mediated by a novel pathway encompassing the tyrosine kinases Src and Syk that activated the downstream kinase proline-rich tyrosine kinase 2. Proline-rich tyrosine kinase 2, in turn, caused activation of the MAPK ERK, thereby triggering SOCS1 induction. SOCS1 did not modulate Dectin-1 signaling but affected TLR signaling, leading to decreased and abbreviated NF-κB activation in BMMs triggered by TLR9. Furthermore, IL-12 and IL-10 secretion were inhibited by SOCS1. We additionally observed that IL-17-producing Th cells were clearly increased by SOCS1 in BMMs. Our results show that SOCS1 is expressed via a new, NF-κB-independent pathway in Dectin-1-triggered murine BMMs and influences TLR cross talk and T cell priming. |
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| Item Description: | Gesehen am 16.04.219 |
| Physical Description: | Online Resource |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.1103068 |