Receptor Cross-Linking on Human Plasmacytoid Dendritic Cells Leads to the Regulation of IFN-α Production

Fanning, Stacey L.; George, Thaddeus C.; Feng, Di; Feldman, Steven B.; Megjugorac, Nicholas J.; Izaguirre, Alexander G.; Fitzgerald-Bocarsly, Patricia

doi:10.4049/jimmunol.177.9.5829

Cited by 89 publications

(93 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In line with our findings, previous work has shown that receptor cross-linking can regulate leukocyte function. Specifically, Fanning et al (24) found that positive selection procedures using a magnetic bead cell isolation kit to obtain pure populations of plasmacytoid dendritic cells led to the inhibition of IFN-␣ production in response to viral stimulation. Together these results highlight the importance of appropriate cell preparation techniques for replicating physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

Natural killer cells actively patrol peripheral lymph nodes forming stable conjugates to eliminate MHC-mismatched targets

Garrod¹,

Wei²,

Parker

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

motility ͉ two-photon microscopy N atural killer (NK) cells are a specialized subset of lymphocytes capable of mediating effector functions without the need for prior sensitization. To avoid aberrant autoimmune attack, NK cells express a diverse repertoire of inhibitory receptors that suppress lytic activity. Polymorphic Ly49 molecules specific for self-MHC class I constitute one of the best characterized family of inhibitory receptors (1). Under normal conditions, persistent engagement of Ly49 by cognate selfligands results in recruitment of SHP-1 to the receptor's cytoplasmic immunoreceptor tyrosine-based inhibitory motif domain and subsequent dephosphorylation of activating signaling pathways (2). This inhibition of NK cell effector function is alleviated in the absence of self-molecules and is often the first step in acute rejection of allogeneic grafts. Although NK cellmediated clearance of circulating MHC-mismatched targets is well established (3), the ability of NK cells to migrate to and eliminate allogeneic target cells from peripheral lymph nodes (LN) under homeostatic conditions remains poorly defined.Recent evidence suggests that NK cells may exert important functional responses within LN. Specifically, enhanced recruitment of NK cells to antigen-stimulated LN facilitated the induction of a productive immune response (4). Moreover, Chen et al. (5) showed that LN NK cells efficiently lysed tumor cells and suppressed B16 melanoma metastasis to draining LN. These findings suggest that NK cells actively patrol the LN in search of cognate target and transformed cells, perhaps exhibiting robust motility similar to other lymphocyte subsets, such as T and B cells (6, 7). Therefore, it was surprising that NK cells isolated by DX5-positive selection were reported to move with slow velocity (2.75 Ϯ 0.17 m/min) when imaged in LN by two-photon microscopy (8).DX5 is a monoclonal antibody commonly used to identify and isolate murine NK cells. DX5 binds the ␣ 2 -integrin CD49b (9). Integrins are heterodimers comprised of ␣-and ␤-subunits and are of key importance in several complex biological processes, including cell adhesion and migration (10). Experimental evidence indicates that integrin engagement can result in the activation of key signaling events (11). Specifically, cross-linking of ␤ 1 -integrins expressed on human NK cells transduces intracellular signals, leading to the activation of the Ras-MAPK cascade, subsequent IFN-␥ production, and enhanced cytotoxicity (12). Therefore, CD49b cross-linking could induce signaling events that render positively selected NK cells immotile. To investigate this possibility, we used two-photon microscopy to visualize the in situ basal motility of unmanipulated NK cells within intact LN and examine their interaction dynamics with syngeneic and allogeneic B cells. Our results demonstrate that CD49b cross-linking strongly modulates motility, adhesion to collagen, and effector function, whereas unmanipulated NK cells are highly motile and preferentially form stable conjugate...

show abstract

Section: Discussionmentioning

confidence: 99%

Natural killer cells actively patrol peripheral lymph nodes forming stable conjugates to eliminate MHC-mismatched targets

Garrod¹,

Wei²,

Parker

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…On the other hand, there can be a faster depolymerisation of F4 pHMM02 fimbriae than F4 GIS26 fimbriae inside antigen presenting cells, which could influence intracellular signalling. Cross-linking of receptors from antigen presenting cells is reported to have an effect on the regulation of immune responses [33,34] and is more efficient by molecules with a high polymeric nature. The use of antigenic repeats is indeed a known method to improve the immunogenicity of an antigen [35,36].…”

Section: Discussionmentioning

confidence: 99%

The polymeric stability of the Escherichia coli F4 (K88) fimbriae enhances its mucosal immunogenicity following oral immunization

Verdonck

Joensuu

Stuyven

et al. 2008

Vaccine

View full text Add to dashboard Cite

a b s t r a c tOnly a few vaccines are commercially available against intestinal infections since the induction of a protective intestinal immune response is difficult to achieve. For instance, oral administration of most proteins results in oral tolerance instead of an antigen-specific immune response. We have shown before that as a result of oral immunization of piglets with F4 fimbriae purified from pathogenic enterotoxigenic Escherichia coli (ETEC), the fimbriae bind to the F4 receptor (F4R) in the intestine and induce a protective F4-specific immune response. F4 fimbriae are very stable polymeric structures composed of some minor subunits and a major subunit FaeG that is also the fimbrial adhesin. In the present study, the mutagenesis experiments identified FaeG amino acids 97 (N to K) and 201 (I to V) as determinants for F4 polymeric stability. The interaction between the FaeG subunits in mutant F4 fimbriae is reduced but both mutant and wild type fimbriae behaved identically in F4R binding and showed equal stability in the gastro-intestinal lumen. Oral immunization experiments indicated that a higher degree of polymerisation of the fimbriae in the intestine was correlated with a better F4-specific mucosal immunogenicity. These data suggest that the mucosal immunogenicity of soluble virulence factors can be increased by the construction of stable polymeric structures and therefore help in the development of effective mucosal vaccines.

show abstract

“…For instance, transcription factors such as NF-κB can be tracked during translocation from the cytoplasm to the nucleus or various extra-and intracellular molecules/receptors can be analyzed for their co-localization. Classical flow cytometry provides information about the presence of particular molecules in the cell by a characteristic fluorescence signal, while ISS gives additional information about the localization of this signal in the cell [22,29]. The multiple features can be computed and compared not only on the single cell level but also among selected populations.…”

Section: Iss Overviewmentioning

confidence: 99%

“…In Table 3 we summarized selected examples of ISS applications that have been recently published in the literature and some new applications already established in our laboratory. Accordingly, by analogy to LSC, ISS can be used to investigate protein translocations and precisely localize various molecules in cellular compartments [17,22,[29][30][31]. Beyond FC, ISS can be used for morphological characterization of cells as presented in the examples below.…”

Section: Applications Of Issmentioning

confidence: 99%

See 1 more Smart Citation

“Decoding the Dots”: The ImageStream system (ISS) as a novel and powerful tool for flow cytometric analysis

Zuba‐Surma

Kucia

Ratajczak³

2008

Open Life Sciences

View full text Add to dashboard Cite

Abstract:The aim of this article is to provide a brief review of the ImageStream system (ISS). The ISS technology was developed as a novel method for multiparameter cell analysis and subsequently as a supportive tool for flow cytometry (FC). ISS integrates the features of FC and fluorescent microscopy collecting images of acquired cells for offline digital image analysis. The article presents an overview of the main characteristics of ISS and a comparison between ISS, FC and the laser scanning cytometer (LSC). We reviewed ISS applications focusing on those involved in cellular phenotyping and provide our own experience with using ISS as a supportive tool to classical FC and demonstrate the compatibility between FC and ISS photometric analysis as well as the advantages of using ISS to confirm FC results.© Versita Warsaw and Springer-Verlag Berlin Heidelberg.

show abstract

Receptor Cross-Linking on Human Plasmacytoid Dendritic Cells Leads to the Regulation of IFN-α Production

Cited by 89 publications

References 49 publications

Natural killer cells actively patrol peripheral lymph nodes forming stable conjugates to eliminate MHC-mismatched targets

Natural killer cells actively patrol peripheral lymph nodes forming stable conjugates to eliminate MHC-mismatched targets

The polymeric stability of the Escherichia coli F4 (K88) fimbriae enhances its mucosal immunogenicity following oral immunization

“Decoding the Dots”: The ImageStream system (ISS) as a novel and powerful tool for flow cytometric analysis

Contact Info

Product

Resources

About