Splenic dendritic cell involvement in FXR-mediated amelioration of DSS colitis

ABSTRACT Dendritic cells, particularly those residing in the spleen, are thought to orchestrate acquired immunity to malaria, but it is not known how the splenic dendritic cell population responds to malaria infection and how this response compares with the responses of other antigen-presenting cells. We investigated this question for Plasmodium chabaudi AS infection in C57BL/6 mice. We found that dendritic cells, defined here by the CD11c marker, migrated from the marginal zone of the spleen into the CD4+ T-cell area within 5 days after parasites entered the bloodstream. This contrasted with the results observed for the macrophage and B-cell populations, which expanded greatly but did not show any comparable migration. Over the same time period dendritic cells showed upregulation of CD40, CD54, and CD86 costimulatory molecules that are required for successful T-cell activation. In dendritic cells, the peak intracellular gamma interferon expression (as shown by fluorescence-activated cell sorting) was on day 5, 2 days earlier than the peak expression in B-cells or macrophages. These findings show that splenic dendritic cells are actively engaged in the earliest phase of malarial infection in vivo and are likely to be critical in shaping the subsequent immune response.

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Quantitation of corticosterone-induced splenic dendritic cell loss, recovery and prevention in C57BL/6 mice

BIOS ◽

10.1893/0005-3155-91.4.214 ◽

2021 ◽

Vol 91 (4) ◽

Author(s):

Shannon Bessonett ◽

Christine Spiker ◽

Jodi L. Yorty

Keyword(s):

Dendritic Cell ◽

Cell Loss ◽

Loss Recovery ◽

Splenic Dendritic Cell

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Trauma-hemorrhage inhibits splenic dendritic cell proinflammatory cytokine production via a mitogen-activated protein kinase process

AJP Cell Physiology ◽

10.1152/ajpcell.00494.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. C754-C764 ◽

Cited By ~ 9

Author(s):

Takashi Kawasaki ◽

Mashkoor A. Choudhry ◽

Martin G. Schwacha ◽

Satoshi Fujimi ◽

James A. Lederer ◽

...

Keyword(s):

Dendritic Cell ◽

Cytokine Production ◽

Mitogen Activated Protein Kinase ◽

Sham Operation ◽

Dc Functions ◽

Mapk Activation ◽

Midline Laparotomy ◽

Shed Blood ◽

Splenic Dendritic Cell ◽

Mitogen Activated Protein

Although splenic dendritic cell (DC) functions are markedly altered following trauma-hemorrhage, the mechanism(s) responsible for the altered DC functions remains unknown. We hypothesized that trauma-hemorrhage inhibits DC function via suppressing toll-like receptor 4 (TLR4) expression and mitogen-activated protein kinases (MAPKs). To examine this, male C3H/HeN (6–8 wk) mice were randomly assigned to sham operation or trauma-hemorrhage. Trauma-hemorrhage was induced by midline laparotomy and ∼90 min of hypotension [blood pressure (BP) 35 mmHg], followed by fluid resuscitation (4× the shed blood volume in the form of Ringer lactate). Two hours later, mice were euthanized, splenic DCs were isolated, and the changes in their MAPK activation, TLR4-MD-2 expression, and ability to produce cytokines were measured. The results indicate that trauma-hemorrhage downregulated the lipopolysaccharide (LPS)-induced MAPK activation in splenic DCs. In addition to the decrease in MAPK activation, surface expression of TLR4-MD-2 was suppressed following trauma-hemorrhage. Furthermore, LPS-induced cytokine production from splenic DCs was also suppressed following trauma-hemorrhage. These findings thus suggest that the decrease in TLR4-MD-2 and MAPK activation may contribute to the LPS hyporesponsiveness of splenic DCs following trauma-hemorrhage. Hyporesponsiveness of splenic DCs was also found after stimulation with the TLR2 agonist zymosan. Our results may thus explain the profound immunosuppression that is known to occur under those conditions.

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Effect of interleukin-15 on depressed splenic dendritic cell functions following trauma-hemorrhage

AJP Cell Physiology ◽

10.1152/ajpcell.00447.2008 ◽

2009 ◽

Vol 296 (1) ◽

pp. C124-C130 ◽

Cited By ~ 6

Author(s):

Takashi Kawasaki ◽

Mashkoor A. Choudhry ◽

Martin G. Schwacha ◽

Kirby I. Bland ◽

Irshad H. Chaudry

Keyword(s):

Dendritic Cell ◽

Antigen Presentation ◽

Ex Vivo ◽

Sham Operation ◽

Dc Functions ◽

Midline Laparotomy ◽

Shed Blood ◽

Cell Functions ◽

Splenic Dendritic Cell ◽

Ifn Γ

Although trauma-hemorrhage (T-H) induces suppressed splenic dendritic cell (DC) maturation and antigen presentation capacity, it remains unclear whether IL-15 modulates splenic DC functions. The aim of this study therefore was to investigate the effect of IL-15 on splenic DC functions after T-H. Male C3H/HeN mice (6–8 wk old) were randomly assigned to T-H or sham operation. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× the shed blood volume in the form of Ringer lactate). Two hours later, mice were killed, splenic DCs were isolated, and the effects of exogenous IL-15 on their costimulatory factors, major histocompatibility class II expression, ability to produce cytokines, and antigen presentation were measured. The results indicate that IL-15 production capacity of splenic DCs was reduced following T-H. Ex vivo exposure to IL-15 attenuated the suppressed production of TNF-α, IL-6, and IFN-γ from splenic DCs following T-H. In addition, expression of surface antigen studies demonstrate that exogenous IL-15 attenuated T-H-induced downregulation of the activation of DC. The suppressed splenic DC antigen presentation function following T-H was also attenuated by IL-15 treatment. Moreover, IL-15 enhanced IL-12-induced IFN-γ production and antigen presentation by splenic DCs. These data suggest that ex vivo treatment with IL-15 following T-H provides beneficial effects on splenic DCs. The depression in IL-15 production by splenic DCs could contribute to the host's enhanced susceptibility to infections following T-H.

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Splenic dendritic cell subsets prime and boost CD8 T cells and are involved in the generation of effector CD8 T cells

Cellular Immunology ◽

10.1016/j.cellimm.2004.03.010 ◽

2004 ◽

Vol 228 (1) ◽

pp. 15-19 ◽

Cited By ~ 12

Author(s):

Shahriar Behboudi ◽

Anne Moore ◽

Adrian V.S Hill

Keyword(s):

T Cells ◽

Dendritic Cell ◽

Cd8 T Cells ◽

Splenic Dendritic Cell ◽

Dendritic Cell Subsets

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Development of thymic and splenic dendritic cell populations from different hemopoietic precursors

Blood ◽

10.1182/blood.v98.12.3376 ◽

2001 ◽

Vol 98 (12) ◽

pp. 3376-3382 ◽

Cited By ~ 114

Author(s):

Li Wu ◽

Angela D'Amico ◽

Hubertus Hochrein ◽

Meredith O'Keeffe ◽

Ken Shortman ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Dendritic Cell ◽

Cell Populations ◽

Lymphoid Tissues ◽

Hemopoietic Precursors ◽

Surface Molecules ◽

Splenic Dendritic Cell ◽

Antigen Presenting ◽

Macrophage Precursors

Abstract The antigen-presenting dendritic cells (DCs) found in mouse lymphoid tissues are heterogeneous. Several types of DCs have been identified on the basis of the expression of different surface molecules, including CD4, CD8α, and DEC-205. Previous studies by the authors showed that the mouse intrathymic lymphoid-restricted precursors (lin−c-kit+Thy-1lowCD4low) can produce DCs in the thymus and spleen upon intravenous transfer, suggesting a lymphoid origin of these DCs. In the current study, the potential for DC production by the newly identified bone marrow (BM) common lymphoid precursors (CLPs), common myeloid precursors (CMPs), and committed granulocyte and macrophage precursors was examined. It was found that both the lymphoid and the myeloid precursors had the potential to produce DCs. All the different DC populations identified in mouse thymus and spleen could be produced by all these precursor populations. However, CLPs produced predominantly the CD4−CD8α+ DCs, whereas CMPs produced similar numbers of CD4−CD8α+ and CD4+CD8α− DCs, although at different peak times. On a per cell basis, the CLPs were more potent than the CMPs at DC production, but this may have been compensated for by an excess of CMPs over CLPs in BM. Overall, this study shows that the expression of CD8α does not delineate the hemopoietic precursor origin of DCs, and the nature of the early precursors may bias but does not dictate the phenotype of the DC product.

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