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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Ly49Q positively regulates type I IFN production by plasmacytoid dendritic cells in an immunoreceptor tyrosine-based inhibitory motif-dependent manner
Journal of Immunology, Volume 190, No. 8, Year 2013
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Description
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-a 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. Copyright © 2013 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Rahim, Mir Munir Ahmed
Canada, Ottawa
University of Ottawa
Tai, Lee Hwa
Canada, Ottawa
Ottawa Hospital Research Institute
Troke, Angela D.
Canada, Ottawa
University of Ottawa
Mahmoud, Ahmad
Canada, Ottawa
University of Ottawa
Saudi Arabia, Madinah
Taibah University
Abou-Samra, Elias
Canada, Ottawa
University of Ottawa
Roy, Justin G.
Canada, Ottawa
University of Ottawa
Mottashed, Amelia
Canada, Ottawa
University of Ottawa
Ault, Nicholas
Canada, Ottawa
University of Ottawa
Corbeil, Chloe
Canada, Ottawa
University of Ottawa
Goulet, Marie Line
Canada, Ottawa
University of Ottawa
Zein, Sima
Canada, Ottawa
University of Ottawa
Egypt, Giza
Faculty of Agriculture
Hamilton-Valensky, Melisa
Canada, Vancouver
Terry Fox Laboratory
Krystal, Gerald
Canada, Vancouver
Terry Fox Laboratory
Kerr, William G.
United States, Syracuse
Suny Upstate Medical University
Toyama-Sorimachi, Noriko
Japan, Tokyo
National Center for Global Health and Medicine
Makrigiannis, Andrew P.
Canada, Ottawa
University of Ottawa
Statistics
Citations: 17
Authors: 16
Affiliations: 7
Identifiers
Doi:
10.4049/jimmunol.1200873
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Cancer
Genetics And Genomics