Increased TLR responses in dendritic cells lacking the ITAM‐containing adapters DAP12 and FcRγ

Chu, Ching-Liang; Yu, Y. L.; Shen, Kuan-Yin; Lowell, Clifford A.; Lanier, Lewis L.; Hamerman, Jessica A.

doi:10.1002/eji.200737600

Cited by 53 publications

(71 citation statements)

References 39 publications

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“…Attenuation of NF-B activation and down-regulation of TLR4 expression via activating PKA pathway by Fc␥RIIb-dependent PGE 2 may contribute to the suppressive effect of IC/Ig. In addition to Fc␥RIIb, DAP12, FcR␥ chain, and CD32a have also been reported by other studies to exert negative regulatory roles in TLR4 response (37,38), indicating that these physiologically natural IC/Ig may play a critical role in the maintenance of immune homeostasis. Therefore, our results and others outline new mechanistic explanation for clinical administration of IVIg for prevention from serious inflammation or treatment of autoimmune diseases.…”

Section: Discussionmentioning

confidence: 67%

Immune Complex/Ig Negatively Regulate TLR4-Triggered Inflammatory Response in Macrophages through FcγRIIb-Dependent PGE2 Production

Zhang

Liu

et al. 2009

The Journal of Immunology

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Excessive activation of TLR may induce endotoxin shock and inflammatory diseases, so the negative regulation of TLR-triggered inflammatory response attracts much attention. Nonpathogenic immune complex (IC) and Ig (IC/Ig) have been shown to play important roles in the regulation of immune responses and to be therapeutic in some kinds of autoimmune diseases. However, the role of IC/Ig in the regulation of TLR-triggered inflammatory responses and the underlying mechanisms remain to be fully understood. In this study we demonstrate that IC/Ig can significantly inhibit LPS-induced secretion of TNF-␣ and IL-6 from macrophages by preferentially inducing PGE 2 . Pretreatment of mice with IC can protect wild-type mice, but not Fc␥RIIb ؊/؊

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Section: Discussionmentioning

confidence: 67%

Immune Complex/Ig Negatively Regulate TLR4-Triggered Inflammatory Response in Macrophages through FcγRIIb-Dependent PGE2 Production

Zhang

Liu

et al. 2009

The Journal of Immunology

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“…DC maturation was determined by the upregulation of MHC class II and costimulatory molecule expression, as described previously (29). Cells were treated with LPS (100 ng/ml), quercetin (50 mM), LPS plus DMSO (0.2%), or LPS plus quercetin for 16 h and stained with mAbs specific for mouse CD11c, I-A b , CD40, CD80, and CD86 (BioLegend, San Diego, CA) and then analyzed by flow cytometry.…”

Section: Analysis Of DC Maturation and Endocytosismentioning

confidence: 99%

Immunosuppressive Effect of Quercetin on Dendritic Cell Activation and Function

Huang

Cheng

et al. 2010

The Journal of Immunology

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“…Chu et al also recently reported that ITAM-mediated signaling through DAP12, and FcRg inhibited cDC maturation after TLR stimulation [40]. Taken together, these ITIM and ITAM signals may play a role in DC maturation.…”

Section: Discussionmentioning

confidence: 81%

Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation

Toma-Hirano

Namiki²,

Shibata³

et al. 2009

Eur J Immunol

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Ly49Q, a type II C-type lectin expressed on mouse plasmacytoid DC (pDC), contains a single carbohydrate recognition domain in its extracellular region and an ITIM in its cytoplasmic domain. We have identified the MHC class I molecule H-2K b as a Ly49Q ligand, confirming prior reports. Although H-2K b is expressed on essentially all hematopoietic cells, we found that only CpG-stimulated B cells were able to activate Ly49Q. This discovery correlated with our finding that although H-2K b forms clusters on CpG-activated B cells, it is diffusely expressed on resting B cells. Furthermore, CpG-stimulated, but not resting, B cells up-regulated co-stimulatory molecules on pDC. This finding was confirmed by the fact that binding by anti-Ly49Q mAb to Ly49Q led to pDC maturation in vitro. Our results suggest that clustered H-2K b on activated B cells act as ligands for Ly49Q and induce pDC maturation in vitro.Key words: B cell . IFN . Ly49Q . MHC class I . plasmacytoid DC Supporting Information available online IntroductionPlasmacytoid DC (pDC) are a specialized subset of DC responsible for initiating immune responses to viruses [1,2]. They develop in the bone marrow and circulate in the blood before migrating into lymphoid and non-lymphoid organs [1,2], and they exhibit increased recruitment into sites of inflammation [3,4]. pDC detect viruses through TLR7 and TLR9 [5]. In response, they produce large amounts of type I IFN and pro-inflammatory chemokines to direct the innate and adaptive immune responses and to promote cytotoxicity in NK cells and CD8 1 T cells [6]. pDC have also been implicated in promoting monocyte-derived DC maturation, presenting antigen to T cells, inducing Th1 polarization [1,2], and promoting B-cell differentiation into 1344Ab-producing plasma cells [7,8]. However, there is very little information about how other cells affect pDC function.Ly49Q is a member of the Ly49 family of mouse NK receptors that is expressed on pDC but not on NK cells or NKT cells [9][10][11]. This receptor family belongs to a group of type II integral membrane proteins that contain external domains homologous to the super-family of Ca-dependent lectins [12]. The Ly49 family comprises two subclasses, one of which harbors an ITIM in the cytoplasmic domain, which recruits the intracellular tyrosine phosphatases SHP-1 or SHP-2 [13][14][15]. Members of the other subclass lack an ITIM, have a charged residue in the transmembrane domain, and deliver activating signals via the adapter protein DAP12 [16]. Inhibitory Ly49 molecules primarily bind MHC class I ligands [17,18], whereas the ligands for activating Ly49 molecules also include MHC class I-like molecules expressed by viruses. For example, Ly49H binds the m157 gene product of mouse cytomegalovirus [19,20]. A fine balance between inhibitory and activating signals regulates the cytokine production and cytolytic activity of NK cells [21][22][23].The presence of an ITIM in the cytoplasmic domain of Ly49Q suggests that it -like the Ly49 family members expressed on NK cells -might f...

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Increased TLR responses in dendritic cells lacking the ITAM‐containing adapters DAP12 and FcRγ

Cited by 53 publications

References 39 publications

Immune Complex/Ig Negatively Regulate TLR4-Triggered Inflammatory Response in Macrophages through FcγRIIb-Dependent PGE2 Production

Immune Complex/Ig Negatively Regulate TLR4-Triggered Inflammatory Response in Macrophages through FcγRIIb-Dependent PGE2 Production

Immunosuppressive Effect of Quercetin on Dendritic Cell Activation and Function

Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation

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