CD83 localization in a recycling compartment of immature human monocyte-derived dendritic cells

Klein, Elisabeth; Koch, Susanne; Borm, Bodo; Neumann, Jürgen; Herzog, Volker; Koch, Norbert; Bieber, Thomas

doi:10.1093/intimm/dxh228

Cited by 34 publications

(42 citation statements)

References 36 publications

(40 reference statements)

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“…Indeed increased surface expression of CD83 in DCs from WT mice could be induced already 2 minutes after the addition of the RyR1 agonist caffeine. These results are in line with the finding that CD83 molecules recycle between endosomes and the cell surface (Klein et al, 2005); in endosomes they co-localize with MHC class II molecules and we have previously shown that pharmacological stimulation of RyR1 results in the rapid expression of pre-formed MHC class II molecules on the cell surface (Vukcevic et al, 2008). Taken together these results support the observations that DC maturation results from the convergence of different signals arising from cytokine release, RyR1-activation and NFkB translocation (Bracci et al, 2007;Baeuerle and Henkel, 1994;Frantz et al, 1994).…”

Section: Discussionsupporting

confidence: 92%

Gain of function of the immune system caused by a ryanodine receptor 1 mutation

Vukcevic

Zorzato

Keck

et al. 2013

Journal of Cell Science

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SummaryMutations in RYR1, the gene encoding ryanodine receptor 1, are linked to a variety of neuromuscular disorders including malignant hyperthermia (MH), a pharmacogenetic hypermetabolic disease caused by dysregulation of Ca 2+ in skeletal muscle. RYR1 encodes a Ca 2+ channel that is predominantly expressed in skeletal muscle sarcoplasmic reticulum, where it is involved in releasing the Ca 2+ necessary for muscle contraction. Other tissues, however, including cells of the immune system, have been shown to express ryanodine receptor 1; in dendritic cells its activation leads to increased surface expression of major histocompatibility complex II molecules and provides synergistic signals leading to cell maturation. In the present study, we investigated the impact of an MH mutation on the immune system by studying the RYR1 Y522S knock-in mouse. Our results show that there are subtle but significant differences both in resting 'non-challenged' mice as well as in mice treated with antigenic stimuli, in particular the knock-in mice: (i) have dendritic cells that are more efficient at stimulating T cell proliferation, (ii) have higher levels of natural IgG 1 and IgE antibodies, and (iii) are faster and more efficient at mounting a specific immune response in the early phases of immunization. We suggest that some gain-of-function MH-linked RYR1 mutations might offer selective immune advantages to their carriers. Furthermore, our results raise the intriguing possibility that pharmacological activation of RyR1 might be exploited for the development of new classes of vaccines and adjuvants.

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Section: Discussionsupporting

confidence: 92%

Gain of function of the immune system caused by a ryanodine receptor 1 mutation

Vukcevic

Zorzato

Keck

et al. 2013

Journal of Cell Science

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“…2B). We also identified an EGFP ϩ mCD83 Ϫ DC population that represents immature DCs, consistent with previous reports in which intracellular pools of CD83 were found in the Golgi complex and endocytic vesicles of immature and mature DCs (33,34). However, in contrast to the findings of Cao et al (34), we did not detect CD83 promoter activity in CD11c Ϫ monocytes/macrophages (Fig.…”

Section: Discussionsupporting

confidence: 91%

The CD83 reporter mouse elucidates the activity of the CD83 promoter in B, T, and dendritic cell populationsin vivo

Lechmann

Shuman

Wakeham

et al. 2008

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

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CD83 is the major surface marker identifying mature dendritic cells (DCs). In this study, we report the generation of reporter mice expressing EGFP under the control of the CD83 promoter. We have used these mice to characterize CD83 expression by various immune system cell types both in vivo and ex vivo and under steady-state conditions and in response to stimulation with a Toll-like receptor (TLR) ligand. With those mice we could prove in vivo that the CD83 promoter is highly active in all DCs and B cells in lymphoid organs. Interestingly, this promoter activity in B cells mainly depended on the stage of development, is up-regulated in the late pre-B cell stage, and was maintained on a high level in all peripheral B cells. We also confirmed that CD83 in those cells is mainly intracellular but is up-regulated after TLR stimulation. Otherwise, CD83 promoter activity in T cells seemed to depend on stimulation and could be found mainly in CD4 ؉ CD25 ؉ and CD8 ؉ CD25 ؉ T cells and in CD4 ؉ and CD8 ؉ memory cells. In addition, we identified the murine homologues of the human CD83 splice variants. In contrast to those in human, those extremely rare short transcripts were never found without the expression of the highly dominant full-length form. So, the murine CD83 surface expression is mainly regulated posttranslationally in vivo. Our CD83 reporter mice represent a useful mouse model for monitoring the activation status and migration of DCs and lymphocytes under various conditions, and our results provide much needed clarification of the true nature of CD83 promoter activity.immune system ͉ mouse model ͉ intravital microscopy T he primary cells mediating adaptive responses are T and B lymphocytes and dendritic cells (DCs). A DC's ontogeny, state of differentiation, and degree of maturation governs its expression of a plethora of membrane-bound and soluble molecules that can induce immunostimulatory and immunosuppressive responses (1-3). Maturing DCs up-regulate certain cell surface molecules that greatly enhance their ability to present antigen and activate naive CD4 ϩ and CD8 ϩ T cells. Among these molecules is CD83, first described by Zhou et al. (4), CD83 is one of the most useful markers for identifying mature DCs capable of activating naïve T cells (5-8). CD83 expression also occurs on certain T cell subsets (9, 10), B cells (10-12), and murine thymic epithelial cells (13,14). Studies of CD83 transcription have shown that it is mediated by NF-B during the induction of adaptive responses (15,16).CD83 is conserved from fish species to mammals (17), with mouse CD83 sharing 63% amino acid identity with human CD83 (18,19). To date, two protein isoforms of CD83 have been reported in humans: a membrane-bound form (mCD83) (5) and a soluble form (sCD83) (20). mCD83 is a highly glycosylated surface protein of the Ig superfamily with a molecular mass of 40-45 kDa (5, 21). mCD83 contains an extracellular Ig-like V domain at the N terminus, a short intracellular cytoplasmic domain of 39 aa, and one transmembrane domain (5). ...

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“…Interestingly, the increase in the binding of CD22, or the ␣2,6-specific plant lectin SNA, did not correlate with the expression of the enzyme involved in the synthesis of its glycan, ST6Gal-1, which decreased dramatically. This could be explained by the maturation-triggered mobilization of molecules stored in granules, a phenomenon that has been previously described on DC (56,57), and needs to be further investigated. The interaction between DC and B lymphocytes has been shown to result in multiple effects, such as the inhibition of B cell apoptosis (58), blockage of the production of IgE (59), or Ag presentation (60).…”

Section: Discussionmentioning

confidence: 79%