Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 648-655 ◽  
Author(s):  
Arthur Kaser ◽  
Susanne Kaser ◽  
Nicole C. Kaneider ◽  
Barbara Enrich ◽  
Christian J. Wiedermann ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Receptor Expression ◽  
Interleukin 18 ◽  
Th2 Response ◽  
Th1 Response ◽  
Initiation Phase ◽  
Helper Cell Type

Abstract In vivo evidence suggests that interleukin-18 (IL-18) shapes the development of adaptive immunity toward T-helper cell type 1 (Th1) responses. Monocyte-derived dendritic cells 1 (DC1s) preferentially induce a Th1 response, while plasmacytoid DC-derived DC2s have been linked to a Th2 response. We analyzed the role of IL-18 during the initiation phase of a Th response in vitro to elucidate the basis of these in vivo observations. IL-18 was constitutively released from DC1s, but not DC2s. Neutralization of IL-18 in coculture experiments of DC1s with allogeneic naive T lymphocytes did not alter the Th1/Th2 phenotype, while anti–IL-12 efficiently down-regulated the Th1 response. Unexpectedly, IL-18 receptor (IL-18R) α and β chains were expressed on DC2 lineage. IL-18R expression was functional, as IL-18 induced chemotaxis in plasmacytoid DCs (pre-DC2s) and enhanced the allostimulatory capacity of IL-3–differentiated DC2s. Pre-DC2s exposed to IL-18 skewed the development of Th cells toward Th1 in coculture experiments of DC2s and allogeneic naive T cells, which was inhibited by IL-12 p70 neutralization. IL-18 might have a profound role during the initiation phase of an immune response by recruiting pre-DC2s and modulating the function of DC2s.

scholarly journals In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5

Pituitary ◽  
2010 ◽  
Vol 14 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Federico Gatto ◽  
Federica Barbieri ◽  
Lara Castelletti ◽  
Marica Arvigo ◽  
Alessandra Pattarozzi ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Receptor Expression ◽  
Octreotide Lar ◽  
In Vitro Response

Dendritic cell-derived IL-2 production is regulated by IL-15 in humans and in mice

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 697-702 ◽  
Author(s):  
Sonia Feau ◽  
Valeria Facchinetti ◽  
Francesca Granucci ◽  
Stefania Citterio ◽  
David Jarrossay ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Molecular Mechanisms ◽  
Interleukin 2 ◽  
Adaptive Immune ◽  
Deficient Mice ◽  
Mouse System

Abstract Dendritic cells (DCs) are involved in the initiation and regulation of innate and adaptive immune responses. Several molecular mechanisms regulate these diverse DC functions, and we have previously reported that mouse dendritic cells (mDCs) can produce interleukin-2 (IL-2) in vitro and in vivo, in response to microbial activation and T-cell-mediated stimuli. This property is shared by different DC subtypes, including Langerhans cells. Here we show that, on appropriate stimulation, human DCs, both plasmacytoid and myeloid subtypes, also express IL-2. Interestingly, the production of IL-2 by myeloid DCs is induced by T-cell-mediated stimuli and depends on the presence of IL-15. The key role of this cytokine in regulating IL-2 production was also confirmed in the mouse system. In particular, we could show that DCs from IL-15-deficient mice were strongly impaired in the ability to produce IL-2 after interactions with different microbial stimuli. Our results indicate that DC-produced IL-2 is tightly coregulated with the expression of IL-15.

scholarly journals COX-2 mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla

2014 ◽  
Vol 307 (1) ◽  
pp. F25-F32 ◽  
Author(s):  
Fei Wang ◽  
Xiaohan Lu ◽  
Kexin Peng ◽  
Li Zhou ◽  
Chunling Li ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Renal Medulla ◽  
Receptor Expression ◽  
Ang Ii ◽  
Cox 2 ◽  
Renin Content

(Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where it is activated by angiotensin II (ANG II), resulting in increased renin activity in the renal medulla thereby amplifying the de novo generation and action of local ANG II. The goal of the present study was to test the role of cycloxygenase-2 (COX-2) in meditating ANG II-induced PRR expression in the renal medulla in vitro and in vivo. Exposure of primary rat inner medullary collecting duct cells to ANG II induced sequential increases in COX-2 and PRR protein expression. When the cells were pretreated with a COX-2 inhibitor NS-398, ANG II-induced upregulation of PRR protein expression was almost completely abolished, in parallel with the changes in medium active renin content. The inhibitory effect of NS-398 on the PRR expression was reversed by adding exogenous PGE2. A 14-day ANG II infusion elevated renal medullary PRR expression and active and total renin content in parallel with increased urinary renin, all of which were remarkably suppressed by the COX-2 inhibitor celecoxib. In contrast, plasma and renal cortical active and total renin content were suppressed by ANG II treatment, an effect that was unaffected by COX-2 inhibition. Systolic blood pressure was elevated with ANG II infusion, which was attenuated by the COX-2 inhibition. Overall, the results obtained from in vitro and in vivo studies established a crucial role of COX-2 in mediating upregulation of renal medullary PRR expression and renin content during ANG II hypertension.

scholarly journals Reduction of IL-17A Might Suppress the Th1 Response and Promote the Th2 Response by Boosting the Function of Treg Cells during Silica-Induced Inflammatory ResponseIn Vitro

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Wen Tang ◽  
Fangwei Liu ◽  
Ying Chen ◽  
Laiyu Song ◽  
Wujing Dai ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Diseases ◽  
Treg Cells ◽  
Th2 Response ◽  
Th17 Response ◽  
Th1 Response ◽  
Different Types ◽  
Th17 Cytokine

Silica inhalation can induce chronic lung inflammation and fibrosis. Upon silica stimulation, activated macrophages trigger the T-lymphocyte which can differentiate into many different types of Th cells, including the recently discovered Th17 cells. IL-17A, the typical Th17 cytokine, is reported in some inflammatory diseases. However, the role of IL-17A in silica-induced inflammatory response is still not clear. The regulatory mechanism of silica-induced Th17 response also needs to be investigated. So we established a mice primary cell coculture system (macrophage and lymphocyte) to investigate the role of IL-17A in silica-induced inflammatory responsein vitro, by using anti-IL-17A mAb and IL-1Ra. Both anti-IL-17A mAb and IL-1Ra decreased the level of IL-17A and increased the function of Treg cells. The Th1 response was suppressed and the Th2 response was promoted by the addition of anti-IL-17A mAb or IL-1Ra. IL-1Ra treatment decreased the level of IL-6, whereas the levels of IL-23 and ROR-γt were increased. Our study demonstrated that IL-17A reduction altered the pattern of silica-induced Th responses by boosting the function of Treg cellsin vitro. Blocking the function of IL-1 signal pathway could suppress the level of IL-17A, which played the major role in modulating silica-induced Th responsesin vitro.

The Pten/PI3K pathway governs the homeostasis of Vα14iNKT cells

Blood ◽  
2006 ◽  
Vol 109 (8) ◽  
pp. 3316-3324 ◽  
Author(s):  
Hiroyuki Kishimoto ◽  
Toshiaki Ohteki ◽  
Nobuyuki Yajima ◽  
Koichi Kawahara ◽  
Miyuki Natsui ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Suppressor ◽  
Pi3k Pathway ◽  
Melanoma Cells ◽  
Receptor Expression ◽  
Cytokine Secretion ◽  
Pten Mutation ◽  
Human Cancers

Abstract The tumor suppressor PTEN is mutated in many human cancers. We previously used the Cre-loxP system to generate mice (LckCrePten mice) with a Pten mutation in T-lineage cells. Here we describe the phenotype of Pten-deficient Vα14iNKT cells. A failure in the development of Vα14iNKT cells occurs in the LckCrePten thymus between stage 2 (CD44highNK1.1−) and stage 3 (CD44highNK1.1+), resulting in decreased numbers of peripheral Vα14iNKT cells. In vitro, Pten-deficient Vα14iNKT cells show reduced proliferation and cytokine secretion in response to αGalCer stimulation but enhanced inhibitory Ly49 receptor expression. Following interaction with dendritic cells (DCs) loaded with αGalCer, Pten-deficient Vα14iNKT cells demonstrate activation of PI3K. Indeed, the effects of the Pten mutation require intact function of the PI3K subunits p110γ and p110δ. In vivo, LckCrePten mice display reduced serum IFNγ after αGalCer administration. Importantly, Vα14iNKT cell–mediated protection against the metastasis of melanoma cells to the lung was impaired in the absence of Pten. Thus, the Pten/PI3K pathway is indispensable for the homeostasis and antitumor surveillance function of Vα14iNKT cells.

Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL)

Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3926-3931 ◽  
Author(s):  
Renato Zambello ◽  
Tamara Berno ◽  
Giovanna Cannas ◽  
Ilenia Baesso ◽  
Gianni Binotto ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Specific Antigen ◽  
Cell Types ◽  
Lymphoproliferative Disease ◽  
Topographic Organization ◽  
Functional Analyses ◽  
Granular Lymphocytes

We investigated whether dendritic cells (DCs) play a role in favoring granular lymphocyte (GL) proliferation in patients with lymphoproliferative disease of granular lymphocytes (LDGL). The presence of in vivo circulating DCs was studied in 11 patients (5 CD3+ and 6 CD3- LDGL). Autologous immature (iDCs) and mature (mDCs) DCs generated in vitro were studied for stimulatory activity on cell proliferation of CD3+ and CD3- GLs. The topographic organization of GLs and DCs was also studied in bone marrow (BM) biopsies. Peripheral blood (PB) CD3- GLs from patients showed significant proliferative activity in the presence of iDCs and mDCs. Conversely, monoclonal CD3+ GLs were unresponsive to autologous and allogeneic PB DCs. Analysis of BM biopsies demonstrated a topographic distribution of DCs and GLs that indicates contact between the 2 cell types. On functional assays, DCs obtained from BM were more efficient than PB DCs in stimulating CD3- GLs, and surprisingly, a low but definite stimulatory effect was demonstrated also on CD3+ GLs. The putative contact between DCs and GLs in the BM and, more crucial, the proliferative response of discrete GL populations to DC stimulation suggest the presence of a specific antigen within BM DCs, providing evidence for a role of DCs in the pathogenesis of LDGL.

scholarly journals RAB43 facilitates cross-presentation of cell-associated antigens by CD8α+ dendritic cells

2016 ◽  
Vol 213 (13) ◽  
pp. 2871-2883 ◽  
Author(s):  
Nicole M. Kretzer ◽  
Derek J. Theisen ◽  
Roxane Tussiwand ◽  
Carlos G. Briseño ◽  
Gary E. Grajales-Reyes ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Normal Development ◽  
Specific Monoclonal Antibody ◽  
Cross Presentation ◽  
Conditional Deletion ◽  
Cytoplasmic Vesicles ◽  
Antigen Presenting

In this study, to examine cross-presentation by classical dendritic cells (DCs; cDCs), we evaluated the role of RAB43, a protein found to be selectively expressed by Batf3-dependent CD8α+ and CD103+ compared with other DC subsets and immune lineages. Using a specific monoclonal antibody, we localized RAB43 expression to the Golgi apparatus and LAMP1− cytoplasmic vesicles. Mice with germline or conditional deletion of Rab43 are viable and fertile and have normal development of cDCs but show a defect for in vivo and in vitro cross-presentation of cell-associated antigen. This defect is specific to cDCs, as Rab43-deficient monocyte-derived DCs showed no defect in cross-presentation of cell-associated antigen. These results suggest that RAB43 provides a specialized activity used in cross-presentation selectively by CD8α+ DCs but not other antigen-presenting cells.

scholarly journals Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma

2015 ◽  
Vol 112 (5) ◽  
pp. 1529-1534 ◽  
Author(s):  
Jihyung Lee ◽  
Tae Hoon Kim ◽  
Fiona Murray ◽  
Xiangli Li ◽  
Sara S. Choi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Adenylyl Cyclases ◽  
Th2 Polarization ◽  
Th2 Immunity ◽  
Th2 Differentiation ◽  
G Protein Coupled ◽  
Camp Formation

The inductive role of dendritic cells (DC) in Th2 differentiation has not been fully defined. We addressed this gap in knowledge by focusing on signaling events mediated by the heterotrimeric GTP binding proteins Gαs, and Gαi, which respectively stimulate and inhibit the activation of adenylyl cyclases and the synthesis of cAMP. We show here that deletion of Gnas, the gene that encodes Gαs in mouse CD11c+ cells (GnasΔCD11c mice), and the accompanying decrease in cAMP provoke Th2 polarization and yields a prominent allergic phenotype, whereas increases in cAMP inhibit these responses. The effects of cAMP on DC can be demonstrated in vitro and in vivo and are mediated via PKA. Certain gene products made by GnasΔCD11c DC affect the Th2 bias. These findings imply that G protein-coupled receptors, the physiological regulators of Gαs and Gαi activation and cAMP formation, act via PKA to regulate Th bias in DC and in turn, Th2-mediated immunopathologies.

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