ITAM signaling negatively regulates dendritic cell function via SOCS-1 (116.19)
| Autor: | Hiroaki Ito, Laura Lau, Jessica Hamerman |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:116.19-116.19 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Dendritic cells (DCs) play a crucial role in both the innate and adaptive immune system. DCs use several receptor systems to recognize pathogens, including Toll-like receptors (TLR). We have found that two immunoreceptor tyrosine-based activation motif (ITAM) adaptors (DAP12 and FcRγ) negatively regulate TLR responses in DCs, however the precise mechanism by which ITAM signaling suppresses TLR responses remains to be elucidated. Here, we show that aberrant SOCS-1 expression was found in ITAM signaling-deficient DCs. SOCS-1 is a well-described suppressor for TLR signaling as well as cytokine signaling, including signaling from the IFN-γ and IFN-α/β receptors. We found decreased SOCS-1 expression in DAP12/FcRγ-deficient BM-derived DCs (BMDCs) in comparison with WT BMDCs before and after TLR stimulation at both mRNA and protein levels. MHC class II expression on DAP12/FcRγ-deficient BMDCs was higher than that of WT BMDCs even under steady state conditions, similar to SOCS-1 deficient DCs. Consistent with the decrease of SOCS-1 expression in DAP12/FcRγ-deficient BMDCs, STAT-1 phosphorylation was increased in DAP12/FcRγ-deficient BMDCs upon IFN-γ stimulation in comparison with WT BMDCs. These results suggest that ITAM signaling positively regulates SOCS-1 expression to inhibit DC activation. |
| Databáze: | OpenAIRE |
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