Open Access
Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. - eScholarship
Jessica A. Hamerman,Nadia K. Tchao,Clifford A. Lowell,Lewis L. Lanier +3 more
- Vol. 6, Iss: 6, pp 579-586
Reads0
Chats0
TLDR
This article examined the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs) and found that one or more DAP-pairing receptors negatively regulate signaling through TLRs.Abstract:
DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli. Additionally, macrophages deficient in spleen tyrosine kinase (Syk), which signals downstream of DAP12, showed a phenotype identical to that of DAP12-deficient macrophages. DAP12-deficient mice were more susceptible to endotoxic shock and had enhanced resistance to infection by the intracellular bacterium Listeria monocytogenes. These data suggest that one or more DAP12-pairing receptors negatively regulate signaling through TLRs.read more
Citations
More filters
Journal ArticleDOI
Microglial TYROBP/DAP12 in Alzheimer’s disease: Transduction of physiological and pathological signals across TREM2
TL;DR: In this article , the authors provide an overview of evidence indicating that the biology of the TYROBP extends beyond its interaction with these four ligand-binding ectodomain-intramembranous domain molecules.
Journal ArticleDOI
The biology of TREM receptors
TL;DR: The triggering receptor expressed on myeloid cells (TREM) family of receptors have been investigated in many different disease settings, including inflammatory diseases, autoimmunity, neurodegeneration and cancer as mentioned in this paper .
Dissertation
Nouveaux régulateurs de la signalisation TLR2-NF-kB
TL;DR: In this paper, le role of TLR2-NF-kB in lignees myeloides reaction is investigated, and the composition of complexes multimoleculaires d'activation au sein des radeaux lipidiques.
Journal ArticleDOI
Syk Facilitates Influenza A Virus Replication by Restraining Innate Immunity at the Late Stage of Viral Infection
Yingying Li,Shasha Liu,Yuhai Chen,Biao Chen,Meng Xiao,Kuldeep Rai,Mohamed Maarouf,Gui-Rong Guo,Ji-Long Chen +8 more
TL;DR: Surprisingly, a time course study showed that Syk suppressed innate immunity during late phases of IAV infection and thereby promoted IAV replication, providing new insights into complicated mechanisms underlying interaction between virus and host immune system.
References
More filters
Journal ArticleDOI
A novel immunoglobulin-like transcript from rainbow trout with two Ig-like domains and two isoforms.
Holger Kock,Uwe Fischer +1 more
TL;DR: A first rainbow trout NILT sequence is reported, alternatively spliced into a long membrane-bound and a short, putatively secreted form, both with the same two immunoglobulin (Ig)-like domains.
Journal ArticleDOI
TLR-mediated signaling pathways circumvent the requirement for DAP12 in mast cells for the induction of inflammatory mediator release
TL;DR: Data demonstrate that TLR have differential requirements for DAP12 for their function in different cell types and that the inability of TLR to influence mast cell degranulation may be linked to their inability to utilize DAP 12 to recruit Syk.
Journal ArticleDOI
Tetramethylpyrazine attenuates TNF-α-induced iNOS expression in human endothelial cells: Involvement of Syk-mediated activation of PI3K-IKK-IκB signaling pathways.
TL;DR: The data indicate that TMP might repress iNOS expression, at least in part, through its inhibitory effect of Syk-mediated PI3K phosphorylation in TNF-α-stimulated HUVECs.
Journal ArticleDOI
DAP12 Deficiency in Liver Allografts Results in Enhanced Donor DC Migration, Augmented Effector T Cell Responses and Abrogation of Transplant Tolerance
Osamu Yoshida,Shoko Kimura,Lei Dou,Lei Dou,Benjamin M. Matta,Shinichiro Yokota,Mark A. Ross,David A. Geller,Angus W. Thomson +8 more
TL;DR: DAP12 expression in liver grafts regulates donor mDC migration to host lymphoid tissue, alloreactive T cell responses and transplant tolerance.
Journal ArticleDOI
Contributions of triggering-receptor-expressed-on-myeloid-cells-2 to neurological diseases.
TL;DR: Findings from this review may provide novel insights and opportunities to consider, especially for clinicians, as they diagnose and treat certain neurological diseases.