| First Author | Eberle ME | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 11 | Pages | 5644-54 |
| PubMed ID | 22547696 | Mgi Jnum | J:188728 |
| Mgi Id | MGI:5441668 | Doi | 10.4049/jimmunol.1103068 |
| Citation | Eberle ME, et al. (2012) Dectin-1 stimulation induces suppressor of cytokine signaling 1, thereby modulating TLR signaling and T cell responses. J Immunol 188(11):5644-54 |
| abstractText | 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-kappaB 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-kappaB-independent pathway in Dectin-1-triggered murine BMMs and influences TLR cross talk and T cell priming. |
