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
Dissertation
Modulation de la réponse immunitaire par TLR7: rôle dans le diabète de type 1 et l'asthme allergique.
TL;DR: Nous travaux ont permis de mettre en evidence that le ciblage des voies de signalisation TLR permet de moduler les reponses immunitaires, et notamment celles dues a une perte of tolerance comme dans le cas of desordres immunologiques.
Journal ArticleDOI
The transmembrane adapter SCIMP recruits tyrosine kinase Syk to phosphorylate Toll-like receptors to mediate selective inflammatory outputs
Liping Liu,Richard Lucas,Jeffrey D. Nanson,Yan Li,Jason H. Whitfield,James E. B. Curson,Neeraj Tuladhar,Kirill Alexandrov,Mehdi Mobli,Matthew J. Sweet,Bostjan Kobe,Jennifer L. Stow,Lin Luo +12 more
TL;DR: In this article , the role of SCIMP in mediating the interaction between Syk and TLRs has not yet been investigated, but it has been shown that SCIMp recruits Syk in response to lipopolysaccharide-mediated TLR4 activation, which can contribute to inflammation through selective TLR-driven inflammatory responses.
Tyrosine phosphorylation and structural requirements mediate Toll-like receptor 9 function
TL;DR: It is demonstrated that Syk is important for the intracellular trafficking and exocytosis of the proinflammatory cytokine TNFa, but not IL-6, following CpG stimulation, which implicate this signaling pathway in a novel role of cytokine sorting and may have broader implications for release of other cytokines downstream of various pattern recognition receptors.
Journal Article
Binding of Anionic Ligands to Peptic Fragments of Bovine Serum Albumin
TL;DR: It is concluded that P-A is the fragment with a strong binding site for anionic ligands, but few if any weak sites, while P-B contains multiple weak sites and no strong sites.
References
More filters
Journal ArticleDOI
Toll-like receptor signalling
Shizuo Akira,Kiyoshi Takeda +1 more
TL;DR: Rapid progress that has recently improved the understanding of the molecular mechanisms that mediate TLR signalling is reviewed.
Journal ArticleDOI
An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow.
Manfred B. Lutz,Nicole A. Kukutsch,A. L. J. Ogilvie,Susanne Rössner,Franz Koch,Nikolaus Romani,Gerold Schuler +6 more
TL;DR: This method allows by simple means the generation of high numbers of murine DC with very low B cell or granulocyte contaminations, which will be valuable to study DC biology notably at the molecular level.
Journal ArticleDOI
Positive and Negative Selection of T Cells
TL;DR: The current state of the field regarding the natural ligands and molecular factors required for positive and negative selection are summarized and a model for how these disparate outcomes can be signaled via the same receptor is discussed.
PatentDOI
IRAK-M is a negative regulator of toll-like receptor signaling
TL;DR: IRAK-M regulates TLR signaling and innate immune homeostasis and prevents dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAk-TRAF6 complexes.
Journal ArticleDOI
Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response.
TL;DR: A physiological role for TNF alpha in regulating the development and organization of splenic follicular architecture and in the maturation of the humoral immune response is established.