Expansion of CD4+ CD25+ Foxp3+ T cells by bone marrow‐derived dendritic cells

Marguti, Ivo; Yamamoto, Guilherme Lopes; Costa, Thaís Boccia da; Rizzo, Luiz Vicente; Moraes, Luciana Vieira de

doi:10.1111/j.1365-2567.2008.02927.x

Cited by 25 publications

(27 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Macrophages were co-cultured with C57BL/6 splenocytes at 1:5 (responder/stimulator) ratios (25). The co-cultured cells were incubated for 24-72h with 50μl of ConA (5μg/ml) with or without anti-TIM-3 mAb (effective dose: 10μg/ml) and anti-Gal-9 mAb (effective dose: 20μg/ml).…”

Section: Methodsmentioning

confidence: 99%

T-Cell Immunoglobulin Mucin-3 Determines Severity of Liver Ischemia/Reperfusion Injury in Mice in a TLR4-Dependent Manner

et al. 2010

View full text Add to dashboard Cite

The newly discovered T-cell immunoglobulin mucin (TIM) gene family molecules, expressed by T cells, regulate host immunity and tolerance. Although CD4+ T cells mediate innate immunity-dominated liver ischemia-reperfusion injury (IRI), the underlying mechanisms remain obscure. We have recently documented the novel function of TIM-1 pathway in the mechanism of liver IRI and also found that TLR4 activation plays a key triggering role. Using an anti-TIM-3 Ab, we now studied the role of TIM-3 signaling in the model of partial warm liver ischemia followed by reperfusion. Anti-TIM-3 Ab therapy exacerbated the liver damage, as compared with controls. Histological examination has revealed that anti-TIM-3 Ab augmented the hepatocellular damage, increased local neutrophil infiltration, facilitated local accumulation of T cells/macrophages and promoted liver cell apoptosis. Intrahepatic neutrophil activity, induction of pro-inflammatory cytokines/chemokines and expression of cleaved caspase-3/NF-NB/TLR4 were all increased in the treatment group. In parallel, anti-TIM-3 Ab and anti-galectin-9 (Gal-9; TIM-3 ligand) Ab increased IFN-γ production in ConA-stimulated spleen T cells, and TNFα/IL-6 expression in ConA-stimulated macrophage/T cell co-culture system. Interestingly, anti-TIM-3 Ab treatment did not affect liver IRI in TLR4-deficient (KO) mice. In conclusion, TIM-3 blockade exacerbated local inflammation and liver damage, suggesting importance of TIM-3/Gal-9 signaling in the maintenance of hepatic homeostasis. TIM-3-TLR4 cross regulation determined the severity of liver IRI in TLR4-dependent manner, a novel finding of potential importance to modulate tissue innate vs. adaptive responses in liver transplant patients. Thus, harnessing physiological negative T cell co-stimulation signaling on hepatic T cells may minimize innate immunity-mediated liver tissue damage.

show abstract

Section: Methodsmentioning

confidence: 99%

T-Cell Immunoglobulin Mucin-3 Determines Severity of Liver Ischemia/Reperfusion Injury in Mice in a TLR4-Dependent Manner

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Immature dendritic cells have been implicated in the process of immune tolerance via their ability to induce Treg proliferation and enhance their suppressive function (Marguti et al, 2009). We asked whether SAA, besides its ability to elicit cytokine production in monocytes, can induce their maturation towards dendritic cells.…”

Section: Resultsmentioning

confidence: 99%

“…Although Teff are a major source of IL-2, this cytokine is also produced by various innate immune cells such monocytes, DC, and NK cells. Indeed, IL-2 production by highly phagocytic immature DC can induce Treg proliferation (Marguti et al, 2009). Therefore, it remains possible that production of common-gamma chain and pro-inflammatory cytokines by innate immune cells might be sufficient to reverse Treg anergy during tissue repair or pathogen encounter.…”

Section: Discussionmentioning

confidence: 99%

Serum amyloid A induces mitogenic signals in regulatory T cells via monocyte activation

Nguyen

Macaubas

Truong

et al. 2014

Molecular Immunology

View full text Add to dashboard Cite

Serum amyloid A (SAA) has recently been identified by our group as a mitogen for regulatory T cells (Treg). However, the molecular mechanism by which SAA induces Treg proliferation is unknown. Here we provide evidence that IL-1β and IL-6 are directly involved in the SAA-mediated proliferation of Treg. By engaging its several cognate receptors, SAA induces IL-1β and IL-6 secretion by monocytes and drives them towards a HLA-DRhi HVEMlo phenotype resembling immature dendritic cells, which have been implicated in tolerance generation. This monocyte-derived cytokine milieu is required for Treg expansion, as inhibition of IL-1β and IL-6 abrogate the ability of SAA to induce Treg proliferation. Furthermore, both IL-1β and IL-6 are required for ERK1/2 and AKT signaling in proliferating Treg. Collectively, these results point to a novel mechanism, by which SAA initiates a monocyte-dependent process that drives mitogenic signals in Treg.

show abstract

“…There is a similar requirement for the processing of parenchymal self antigen by host DC in the induction of CD4 + T cell tolerance in tumor. BM-derived DCs from BALB/c mice are able to promote expansion of CD4 + CD25 + Foxp3 + T cells in vitro and that this occurs independent of the maturation state of the DCs as mature and immature cells are capable of expanding the Foxp3 + cell population [38,39]. This immune ignorance and the immune tolerance mechanisms contribute to tumor development.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Bone-Marrow-Derived Endothelial and Immune Cells in a Murine Colitis-Associated Colorectal Cancer Model

et al. 2013

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) can lead to an increased risk of developing colorectal cancer (CRC). The aim of this study was to establish a model for combined bone marrow transplantation (BMT) and colitis-associated colorectal cancer (CAC) and to define the contribution of BM-derived cells during the inflammation associated with carcinogenesis. We established a model for BMT using green fluorescent protein (GFP) transgenic mice, followed by AOM/DSS-induced CAC, and performed confocal microscopy analysis on in vivo living tissue and frozen tumor sections. Our imaging analyses showed that GFP-positive cells extensively infiltrated the tumor stroma and that some WGA and GFP or CD31 and GFP double-positive cells were observed in the lining of tumor vessels. Flow cytometry analysis of the tumor-infiltrating cells showed that the GFP-positive CD11c+ DCs cells were one-third of the GFP+/CD11C- cells, and that half of these DCs (0.96% vs 1.02%) were GFP-positive BM-derived cells. The majority of CD4+ T cells were GFP-negative (12.02% vs 1.9%), and we discovered a novel CD4+ CD11c+ DC subset (0.34% vs 1.64%). In conclusion, we defined the distribution of BM-derived endothelial cells, CD11c+ DCs and CD4+ T cells in tumors. This model might be useful for elucidating the diverse BM-derived cell types and functions during the progression of colitis-associated colorectal cancer.

show abstract

Expansion of CD4⁺ CD25⁺ Foxp3⁺ T cells by bone marrow‐derived dendritic cells

Cited by 25 publications

References 41 publications

T-Cell Immunoglobulin Mucin-3 Determines Severity of Liver Ischemia/Reperfusion Injury in Mice in a TLR4-Dependent Manner

T-Cell Immunoglobulin Mucin-3 Determines Severity of Liver Ischemia/Reperfusion Injury in Mice in a TLR4-Dependent Manner

Serum amyloid A induces mitogenic signals in regulatory T cells via monocyte activation

Distribution of Bone-Marrow-Derived Endothelial and Immune Cells in a Murine Colitis-Associated Colorectal Cancer Model

Contact Info

Product

Resources

About