Ly49Q Positively Regulates Type I IFN Production by Plasmacytoid Dendritic Cells in an Immunoreceptor Tyrosine-Based Inhibitory Motif-Dependent Manner.

Citation:
Rahim MM, T. LH, T. AD, M. AB, A. - S. E, R. JG, M. A, A. N, C. C, Z. HS, et al., "Ly49Q Positively Regulates Type I IFN Production by Plasmacytoid Dendritic Cells in an Immunoreceptor Tyrosine-Based Inhibitory Motif-Dependent Manner.", Journal of Immunology, vol. 190, issue 8, pp. 3994-4004, 2013.

Abstract:

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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-α 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-α 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-α 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.

Notes:

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