| First Author | Rahim MM | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 8 | Pages | 3994-4004 |
| PubMed ID | 23479228 | Mgi Jnum | J:194900 |
| Mgi Id | MGI:5475039 | Doi | 10.4049/jimmunol.1200873 |
| Citation | Rahim MM, et al. (2013) Ly49Q Positively Regulates Type I IFN Production by Plasmacytoid Dendritic Cells in an Immunoreceptor Tyrosine-Based Inhibitory Motif-Dependent Manner. J Immunol 190(8):3994-4004 |
| abstractText | Plasmacytoid dendritic cells (pDC) are the major producers of type I IFN during the initial immune response to viral infection. Ly49Q, a C-type lectin-like receptor specific for MHC-I, possesses a cytoplasmic ITIM and is highly expressed on murine pDC. Using Ly49Q-deficient mice, we show that, regardless of strain background, this receptor is required for maximum IFN-alpha production by pDC. Furthermore, Ly49Q expression on pDC, but not myeloid dendritic cells, is necessary for optimal IL-12 secretion, MHC-II expression, activation of CD4(+) T cell proliferation, and nuclear translocation of the master IFN-alpha regulator IFN regulatory factor 7 in response to TLR9 agonists. In contrast, the absence of Ly49Q did not affect plasmacytoid dendritic cell-triggering receptor expressed on myeloid cells expression or pDC viability. Genetic complementation revealed that IFN-alpha production by pDC is dependent on an intact tyrosine residue in the Ly49Q cytoplasmic ITIM. However, pharmacological inhibitors and phosphatase-deficient mice indicate that Src homology 2 domain-containing phosphatase 1 (SHP)-1, SHP-2, and SHIP phosphatase activity is dispensable for this function. Finally, we observed that Ly49Q itself is downregulated on pDC in response to CpG exposure in an ITIM-independent manner. In conclusion, Ly49Q enhances TLR9-mediated signaling events, leading to IFN regulatory factor 7 nuclear translocation and expression of IFN-I genes in an ITIM-dependent manner that can proceed without the involvement of SHP-1, SHP-2, and SHIP. |
