Endogenously Produced Interleukin 6 is an Accessory Cytokine for Dendritic Cell Hematopoiesis

Santiago‐Schwarz, Frances; Tucci, John; Carsons, Steven E.

doi:10.1002/stem.140225

Cited by 24 publications

(14 citation statements)

References 21 publications

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“…Our data demonstrating that IL-6 inhibits BMDC generation are consistent with several previous findings that IL-6 prevents monocytes from differentiating into DC (11,14). However, Santiago-Schwarz et al (16) showed that when CD34 ϩ progenitor cells were cultured with GM-CSF, TNF-␣, and stem cell factor, the yield of DC was increased in cultures with higher supernatant IL-6 levels and reduced by the addition of an anti-IL-6 Ab. In contrast to our findings of increased BMDC generation from IL-6 Ϫ/Ϫ bone marrow culture in GM-CSF, Brasel et al (15) demonstrated that IL-6 Ϫ/Ϫ bone marrow cultured solely in Flt-3 ligand produced much fewer BMDC than WT bone marrow.…”

Section: Discussionsupporting

confidence: 93%

“…Brasel et al (15) established that blocking IL-6 function reduced the number of DC generated in Flt-3 ligand-supplemented murine wild-type (WT) bone marrow cultures. In another report, higher IL-6 levels correlated with greater DC yield in cultures of CD34 ϩ cells (16). Although DC are known to produce IL-6, data regarding the contribution of IL-6 secretion to DC function are sparse.…”

mentioning

confidence: 97%

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Increased and Long-Term Generation of Dendritic Cells with Reduced Function from IL-6-Deficient Bone Marrow

Bleier

Pillarisetty

Shah

et al. 2004

The Journal of Immunology

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The importance of IL-6 in dendritic cell (DC) development and function has not been well defined. To establish the role of IL-6, we studied bone marrow-derived DC (BMDC) and freshly isolated splenic DC from IL-6−/−-transgenic mice. We found that although IL-6−/− bone marrow had a similar composition to that of wild-type (WT) mice, it generated up to 10 times more DC when cultured in GM-CSF. The difference persisted even when IL-6−/− and WT bone marrow were cultured together, excluding the possibility that the effects were simply due to different cytokine microenvironments. In comparison to WT BMDC, IL-6−/− BMDC captured at least as much Ag, had an equivalent surface phenotype, and matured similarly in response to LPS or CpG. However, IL-6−/− BMDC induced less T cell allostimulation and Ag-specific T cell activation, but only the former was related to their inability to generate IL-6. Although WT bone marrow cultures died within 4 wk, IL-6−/− cultures continued to generate BMDC for >120 days, although the BMDC became immature and less functional. In vivo, we found that IL-6−/− mice had similar numbers and types of splenic DC as WT mice, both normally and after treatment with either Flt-3 ligand or GM-CSF. These findings demonstrate that IL-6 has profound effects on DC development in vitro, although the number and subtype composition of DC are unaffected by the absence of IL-6 in vivo. Furthermore, secretion of IL-6 is critical to certain DC functions.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 97%

Increased and Long-Term Generation of Dendritic Cells with Reduced Function from IL-6-Deficient Bone Marrow

Bleier

Pillarisetty

Shah

et al. 2004

The Journal of Immunology

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“…Even following stimulation with LPS, TNF-α, and Der p, the percentages of CD11c + BMDCs from IL-6 KO mice did not increase as compared to those from WT mice, implying that IL-6 can promote DC generation. In a previous study, IL-6 levels were also positively correlated with DC yield in CD34 + progenitor cell culture [31]. Our results appear to contrast the report of Bleier et al [32], which shows that IL-6 KO BMs generate more CD11c + BMDCs than WT BMs.…”

Section: Discussioncontrasting

confidence: 88%

Critical role of IL-6 in dendritic cell-induced allergic inflammation of asthma

2015

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“…IL-6 is a key cytokine in DC development [32]. IL-6 is also an important inflammatory response mediator in DCs [33], [34].…”

Section: Resultsmentioning

confidence: 99%

“…IFN-γ and IL-12 can be produced by DCs, enhance the antigen presenting capabilities of DCs, and support initiation and modulation of adaptive immune responses [50]. Higher IL-6 levels were correlated with DC content and development [32]. In contrast to S2308, RB51 was able to trigger a potent secretion of TNF-α, IL-12/IL23p40, IFN-γ, and IL-6 from WT BMDCs.…”

Section: Discussionmentioning

confidence: 99%

Caspase-2-Dependent Dendritic Cell Death, Maturation, and Priming of T Cells in Response to Brucella abortus Infection

2012

PLoS ONE

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Smooth virulent Brucella abortus strain 2308 (S2308) causes zoonotic brucellosis in cattle and humans. Rough B. abortus strain RB51, derived from S2308, is a live attenuated cattle vaccine strain licensed in the USA and many other countries. Our previous report indicated that RB51, but not S2308, induces a caspase-2-dependent apoptotic and necrotic macrophage cell death. Dendritic cells (DCs) are professional antigen presenting cells critical for bridging innate and adaptive immune responses. In contrast to Brucella-infected macrophages, here we report that S2308 induced higher levels of apoptotic and necrotic cell death in wild type bone marrow-derived DCs (WT BMDCs) than RB51. The RB51 and S2308-induced BMDC cell death was regulated by caspase-2, indicated by the minimal cell death in RB51 and S2308-infected BMDCs isolated from caspase-2 knockout mice (Casp2KO BMDCs). More S2308 bacteria were taken up by Casp2KO BMDCs than wild type BMDCs. Higher levels of S2308 and RB51 cells were found in infected Casp2KO BMDCs compared to infected WT BMDCs at different time points. RB51-infected wild type BMDCs were mature and activated as shown by significantly up-regulated expression of CD40, CD80, CD86, MHC-I, and MHC-II. RB51 induced the production of cytokines TNF-α, IL-6, IFN-γ and IL12/IL23p40 in infected BMDCs. RB51-infected WT BMDCs also stimulated the proliferation of CD4+ and CD8+ T cells compared to uninfected WT BMDCs. However, the maturation, activation, and cytokine secretion are significantly impaired in Casp2KO BMDCs infected with RB51 or Salmonella (control). S2308-infected WT and Casp2KO BMDCs were not activated and could not induce cytokine production. These results demonstrated that virulent smooth strain S2308 induced more apoptotic and necrotic dendritic cell death than live attenuated rough vaccine strain RB51; however, RB51, but not its parent strain S2308, induced caspase-2-mediated DC maturation, cytokine production, antigen presentation, and T cell priming.

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Endogenously Produced Interleukin 6 is an Accessory Cytokine for Dendritic Cell Hematopoiesis

Cited by 24 publications

References 21 publications

Increased and Long-Term Generation of Dendritic Cells with Reduced Function from IL-6-Deficient Bone Marrow

Increased and Long-Term Generation of Dendritic Cells with Reduced Function from IL-6-Deficient Bone Marrow

Critical role of IL-6 in dendritic cell-induced allergic inflammation of asthma

Caspase-2-Dependent Dendritic Cell Death, Maturation, and Priming of T Cells in Response to Brucella abortus Infection

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