Novel Subset of CD8α+ Dendritic Cells Localized in the Marginal Zone Is Responsible for Tolerance to Cell-Associated Antigens

Qiu, Chun-Hong; Miyake, Yoshihiro; Kaise, Hitomi; Kitamura, Hiroshi; Ohara, Osamu; Tanaka, Masato

doi:10.4049/jimmunol.0803364

Cited by 186 publications

(237 citation statements)

References 52 publications

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“…We have previously shown that injection of cytochrome c selectively kills cross-presenting cells in an Apaf-1 (apoptosome)-dependent way [19], based on the rationale that only cross-presenting cells would translocate cytochrome c from the endosome into the cytosol (where the apoptosome is formed). It has been shown that cytochrome c preferentially kills CD103 hi CD8 1 DCs [7]. We also observed similar findings for CD8 1 DCs from WT and GMtg mice (unpublished data).…”

Section: Discussionsupporting

confidence: 88%

“…For example, in one report, all spleen CD8 1 DCs express high levels of CD103 [18]. In another report, about half of the spleen CD8 1 DC express high levels of CD103 [7]. We find that in our colony of B6 mice, only 10-30% of CD8 1 DCs express appreciable levels of CD103.…”

Section: Discussionmentioning

confidence: 42%

“…The proportion of CD103 1 CD8 1 DCs appears to vary between different mouse colonies. For example, some have described that all splenic CD8 1 DCs express high levels of CD103 [18], whereas others have found that only about half express high levels of CD103 [7]. As we found that GM-CSF can enhance crosspresentation by CD8 1 DCs, we wanted to investigate whether GM-CSF could regulate CD103.…”

Section: Gm-csf Regulates Expression Of Cd103 On Cd8 1 Dcsmentioning

confidence: 94%

“…There is at least one report of CD103 expression on CD8 1 DCs being associated with several functional features related to cross-presentation: uptake of cellular antigen, sensitivity to suicide by exogenous cytochrome c (indicative of cytosolic translocation), and superior ability to stimulate proliferation of CD8 1 T cells [7]. The proportion of CD103 1 CD8 1 DCs appears to vary between different mouse colonies.…”

Section: Gm-csf Regulates Expression Of Cd103 On Cd8 1 Dcsmentioning

confidence: 99%

“…presenting exogenous antigens to CD8 1 T cells) [2][3][4], for the rapid uptake of certain bacterial pathogens [5] and for producing IL-12 [6]. It has been previously reported that a small proportion of CD8 1 DCs express the integrin CD103 and these CD103-expressing CD8 1 DCs are enriched in cells engulfing cellular antigens and cross-priming CD8 1 T cells [7]. However, it is unclear what regulates the above functions of CD8 1 DCs and what controls CD103 expression on CD8 1 DCs.…”

Section: Introductionmentioning

confidence: 99%

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GM‐CSF increases cross‐presentation and CD103 expression by mouse CD8⁺ spleen dendritic cells

et al. 2011

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Resident CD8 1 DCs perform several functions, including cross-presenting antigen and rapidly engulfing the Gram-positive intracellular pathogen Listeria monocytogenes. Little is known about how these functions of CD8 1 DCs are modulated. Here, we show that granulocyte-macrophage CSF (GM-CSF), a cytokine that exists at low levels at steady state but is elevated during infection and inflammation, enhances cross-presentation and rapid uptake of L. monocytogenes by resident CD8 1 DCs. This previously unrecognized functional enhancement of CD8 1 DCs by GM-CSF was independent of promoting DC survival in vitro. Enhancement of these functions by GM-CSF was also marked by CD103 expression on CD8 1 DCs that was strongly regulated by GM-CSF. Our findings not only identify GM-CSF as a key molecule regulating CD8 1 DC function, but also as a factor responsible for functional heterogeneity of CD8 1 DCs that is at least substantially demarcated by CD103 expression.Keywords: CD8 1 DC . CD103 . Cross-presentation . Granulocyte-macrophage colony-stimulating factor . Listeria monocytogenes Supporting Information available online IntroductionDCs found in the spleen can be grossly separated into CD8 1 DCs and CD8 À DCs. The latter includes CD8 À CD4 1 and CD8 À CD4 À conventional DCs and CD45RA 1 plasmacytoid DCs. Different DC subsets have different functions. Notably, the resident CD8 1 DCs show superior capacity for ingesting cell-associated antigens [1], for cross-presenting antigens (i.e. presenting exogenous antigens to CD8 1 T cells) [2][3][4], for the rapid uptake of certain bacterial pathogens [5] and for producing . It has been previously reported that a small proportion of CD8 1 DCs express the integrin CD103 and these CD103-expressing CD8 1 DCs are enriched in cells engulfing cellular antigens and cross-priming CD8 1 T cells [7]. However, it is unclear what regulates the above Ã Co-senior authors. Here, we investigated whether GM-CSF might influence the function of CD8 1 DCs and CD103 expression. Functionally, DCs from GM-CSF transgenic (GMtg) mice had enhanced crosspresentation, whereas in the absence of GM-CSF signaling, crosspresentation was reduced. Rapid uptake of Listeria monocytogenes by CD8 1 DCs was also reduced in the absence of GM-CSF. Phenotypically, we showed that bacterial infection preferentially increased CD103 expression by CD8 1 DCs and this increase was dependent on GM-CSF. Together, our results identify a critical role for GM-CSF in preferentially regulating expression of the integrin CD103 by CD8 1 DCs and in regulating certain functions of CD8 1 DCs. ResultsGM-CSF enhances cross-presentation by CD8 1 DCs GM-CSF is a cytokine that exists at very low levels at steady state but is greatly induced during infection and inflammation [13]. To understand the role of GM-CSF in regulating the functions of CD8 1 DCs, we chose mouse models with GM-CSF overexpression. We first compared the cross-presentation by CD8 1 DCs from GMtg mice and control littermates. When soluble OVA was used as the antigen in vitro, CD...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 42%

Section: Gm-csf Regulates Expression Of Cd103 On Cd8 1 Dcsmentioning

confidence: 94%

Section: Gm-csf Regulates Expression Of Cd103 On Cd8 1 Dcsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GM‐CSF increases cross‐presentation and CD103 expression by mouse CD8⁺ spleen dendritic cells

et al. 2011

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Dendritic Cells

See

Ginhoux

2015

Encyclopedia of Life Sciences

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Dendritic cells (DCs) are distributed in almost all tissues body, acting as sentinels of the immune system. They serve as specialised pathogen‐sensing and antigen‐presenting cells that initiate and regulate the immune response. DCs are derived from unique progenitors present in the bone marrow, which seed the tissues where they differentiate into mature DCs. Transcriptomic, phenotypic and functional analyses indicate that human and murine DCs can be divided into three subsets: two subsets of conventional DCs (cDC) named cDC1 and cDC2, and a third lineage of plasmacytoid DCs (pDCs). Each subset is unique and has distinct functional specialisations to control specific T‐cell responses. DCs form a complex cellular network capable of integrating multiple environmental signals and can induce either immunity or tolerance. As a consequence, DCs are suitable candidates for therapeutic intervention in immune‐mediated conditions. Key Concepts Dendritic cells are a heterogeneous group of specialised pathogen‐sensing and antigen‐presenting cells. They are distributed in almost all tissues and organs, and act as sentinels of the immune system. They are derived from DC‐restricted progenitors present in the bone marrow and arise from a dedicated lineage. They can be grouped into three subsets based on ontogeny and transcription factor dependency: two lineages of conventional DCs named cDC1 and cDC2, as well as a third lineage of plasmacytoid DCs (pDCs). Each subset is unique and has distinct functional specialisations. The cDC1 subset is efficient at cross‐presentation, and elicits Th1 responses. The cDC2 subset is capable of eliciting Th2 and Th17 responses. pDCs produce large amounts of type I interferons to combat viral infections.

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The identification and enumeration of dendritic cell populations from individual mouse spleen and Peyer's patches using flow cytometric analysis

Duriancik

Hoag

2009

Cytometry Pt A

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Dendritic cell (DC) research currently involves pooling of tissues from multiple animals followed by enrichment techniques to obtain sufficient numbers of DCs for analysis. Enrichment techniques take advantage of DC adherence, buoyant density properties, and/or positive or negative selection of cell populations using monoclonal antibodies. However, enrichment techniques may significantly change the maturation and/or activation status of DCs or selectively eliminate one or more subpopulations of DCs. To overcome these drawbacks, we designed a multicolor flow cytometric technique for simultaneous analysis of DC populations from tissues of individual mice. The spleens and Peyer's patches were mechanically and enzymatically digested, then incubated with a panel of six monoclonal antibody-fluorochrome direct conjugate reagents. A BD 1 Biosciences LSR II flow cytometer and FCS Express 1 software were used to identify three subtypes of mature DCs (myeloid, lymphoid, and plasmacytoid), precursor DCs, polymorphonuclear neutrophils, B lymphocytes, and Gr-1 1 /CD8a 1 memory T lymphocytes in the spleen. Likewise, we also identified these DC subpopulations and B lymphocytes in the Peyer's patches. The three key parameters in analysis of the DC populations were bi-exponential plotting in data analysis, collection of a minimum of 50,000 total events, and accurate color compensation. This procedure to analyze DCs from individual mice can lead to further understanding of the role of DCs in many other model systems as well as better understanding of how dietary or physiological factors may affect in vivo DC homeostasis. ' 2009 International Society for Advancement of Cytometry

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Novel Subset of CD8α+ Dendritic Cells Localized in the Marginal Zone Is Responsible for Tolerance to Cell-Associated Antigens

Cited by 186 publications

References 52 publications

GM‐CSF increases cross‐presentation and CD103 expression by mouse CD8⁺ spleen dendritic cells

GM‐CSF increases cross‐presentation and CD103 expression by mouse CD8⁺ spleen dendritic cells

Dendritic Cells

The identification and enumeration of dendritic cell populations from individual mouse spleen and Peyer's patches using flow cytometric analysis

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Novel Subset of CD8α+ Dendritic Cells Localized in the Marginal Zone Is Responsible for Tolerance to Cell-Associated Antigens

Cited by 186 publications

References 52 publications

GM‐CSF increases cross‐presentation and CD103 expression by mouse CD8+ spleen dendritic cells

GM‐CSF increases cross‐presentation and CD103 expression by mouse CD8+ spleen dendritic cells

Dendritic Cells

The identification and enumeration of dendritic cell populations from individual mouse spleen and Peyer's patches using flow cytometric analysis

Contact Info

Product

Resources

About

GM‐CSF increases cross‐presentation and CD103 expression by mouse CD8⁺ spleen dendritic cells

GM‐CSF increases cross‐presentation and CD103 expression by mouse CD8⁺ spleen dendritic cells