Cd11c+B220+Gr-1+ Cells in Mouse Lymph Nodes and Spleen Display Characteristics of Plasmacytoid Dendritic Cells

Nakano, Hideki; Yanagita, Manabu; Gunn, Michael D.

doi:10.1084/jem.194.8.1171

Cited by 631 publications

(549 citation statements)

References 30 publications

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“…39 MoDCs restored highaffinity LFA-1 after migration to the lymph nodes (Figure 2c), suggesting a role for CCL21 in this process. Interestingly, lymph node-resident human DCs also express endogenous CCL21 on the cell surface, further highlighting the relevance of our study in the in vivo situation.…”

Section: Ccl21 Strongly Binds To Dcs and Induces Active Lfa-1mentioning

confidence: 89%

The lymphoid chemokine CCL21 triggers LFA‐1 adhesive properties on human dendritic cells

et al. 2010

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Dendritic cells (DCs) are the most potent APCs, involved in the induction of immunity and tolerance. Recently we showed that during differentiation of human DCs from monocyte precursors, Lymphocyte function-associated antigen-1 (LFA-1)-binding capacity is lost, although integrin expression levels were maintained constant, suggesting a different regulation mechanism of this integrin on different cell types. However, the exact role of LFA-1 in DC adhesion and migration remains obscure. Chemokines are potent regulators of integrin function, influencing migratory and adhesive properties of leukocytes. Here, we show that upon vaccination of cancer patients with human DCs, cells that have migrated in vivo into the lymph nodes upregulated the active form of LFA-1. We further show that exposure of human DCs to the lymphoid chemokine CCL21 specifically restores the high-affinity form of LFA-1 and induces binding to its ligand ICAM-1 under low shear stress. Our data indicate that on DCs LFA-1 may function as an inducible anchor during lymphatic transmigration or within the lymph nodes. A thorough understanding of the adhesive events during the DC life cycle will help to improve the outcome of DC-based antitumor clinical trials. Keywords: integrin; cell adhesion; affinity; migration; antigen-presenting cell Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs), involved in the induction of immunity and tolerance. 1 DCs presenting foreign or self-antigen migrate to the lymph node, a spatially defined compartment that facilitates encounter of APCs with rare Ag-specific naive T and B cells. DCs originate from precursor cells in the blood (for example, monocytes) and are recruited to the tissues by transendothelial migration mediated by integrin-dependent arrest. 2 Several clinical studies exploit monocyte-derived DC (moDCs) vaccines to induce antigen-specific response in cancer patients. 3 Integrins are transmembrane a/b-heterodimers that regulate cell-cell and cell-extracellular matrix interactions. Lymphocyte function-associated antigen-1 (LFA-1, aLb2) is a leukocyte-specific integrin that mediates firm arrest on the endothelium and, within tissues, cell tethering and the formation of the immunological synapse. 4 LFA-1 shifts between bent, low-affinity and variable extended conformations with high affinity to its ligand intercellular adhesion molecule-1 (ICAM-1) and to a lesser extent also to ICAM-2 and ICAM-3. 5 Ligand binding can further be increased by dynamic redistribution of LFA-1 in the cell membrane, a phenomenon designated as avidity regulation. 6,7 In circulating leukocytes, LFA-1 remains largely inactive but becomes activated by endothelium-presented chemokines by signaling through G-protein-coupled receptors and application of shear stress, resulting in the extension of the molecule followed by immediate ligand binding. 8 The role of integrin activation in transendothelial migration has been widely studied. 9 Homing of DCs through the afferent lymphatics to the lymph nodes is still not comple...

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Section: Ccl21 Strongly Binds To Dcs and Induces Active Lfa-1mentioning

confidence: 89%

The lymphoid chemokine CCL21 triggers LFA‐1 adhesive properties on human dendritic cells

et al. 2010

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“…Human pDC have been found clustered around high endothelial venules (HEV) [46]. This anatomical localization and cell surface antigen expression on pDC suggest that pDC migrate from the blood to the lymph nodes through HEV in an L-selectin-dependent manner [47][48][49]. However, it has been reported that CCR7 expression is up-regulated on pDC in response to pathogenic stimuli, and that pDC migrate to the CCR7 ligands CCL19 and CCL21 expressed by stromal cells in the T cell zone and in HEV [29,50,51].…”

Section: Validation Of Pdc Conversion Into Cdcmentioning

confidence: 96%

Type I interferon regulates pDC maturation and Ly49Q expression

Toma-Hirano

Namiki²,

Miyatake

et al. 2007

Eur J Immunol

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Ly49Q is expressed on peripheral mouse plasmacytoid dendritic cells (pDC). Immature Ly49Q-negative pDC precursors acquire Ly49Q in the bone marrow and then migrate into the periphery. While searching for molecules that regulate pDC maturation, we found that type I interferon (IFN) inhibited Ly49Q acquisition in vitro. Infections that induce type I IFN production by cells other than pDC (a condition mimicked by poly(I:C) injection in vivo) increase the prevalence of Ly49Q -pDC in the bone marrow and peripheral lymphoid organs in wild-type but not IFN-a/b receptor knockout BALB/c mice. Moreover, in vivo exposure to type I IFN causes some Ly49Q -, but not Ly49Q + , pDC to convert to conventional DC, defined as B220 -CD11c + CD11b + cells. These data suggest that type I IFN regulates pDC development and affects their distribution in the body.

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“…An important cytokine generated by pDC is type1 interferons (IFN-α/β), which become a characteristic of plasmacytoid DC in both humans and mice [78][79][80]. Mouse lymphoid DC population is characterized by expression of a homodimer of the CD8 molecule.…”

Section: The Roles Of T Regulatory Cells and Dendritic Cells In Ibds mentioning

confidence: 99%

STAT3 in immune responses and inflammatory bowel diseases

2006

Cell Res

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214npg STAT3 has been known as a mediator for gene expression induced by many important cytokines. Recent studies have suggested that STAT3 has important functions in regulation of both innate and adaptive immunity. Loss of STAT3 in immune cells caused severe inflammation in response to pathogens. This review discusses the recent progress and suggests directions for the future research on this interesting molecule.

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Cd11c+B220+Gr-1+ Cells in Mouse Lymph Nodes and Spleen Display Characteristics of Plasmacytoid Dendritic Cells

Cited by 631 publications

References 30 publications

The lymphoid chemokine CCL21 triggers LFA‐1 adhesive properties on human dendritic cells

The lymphoid chemokine CCL21 triggers LFA‐1 adhesive properties on human dendritic cells

Type I interferon regulates pDC maturation and Ly49Q expression

STAT3 in immune responses and inflammatory bowel diseases

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