Dendritic cells pulsed with antigen-specific apoptotic bodies prevent experimental type 1 diabetes

Marín-Gallén, Silvia; Clemente-Casares, Xavier; Planas, Raquel; Pujol‐Autonell, Irma; Carrascal, Jorge; Carrillo, Jorge; Ampudia, Rosa-Maria; Verdaguer, Joan; Pujol-Borrell, Ricardo; Borràs, Francesc E.; Vives-Pi, Marta

doi:10.1111/j.1365-2249.2009.04082.x

Cited by 72 publications

(85 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The capacity of DCs, especially iDCs, to dampen autoimmune reactivity in an Ag-specific manner highlights their potential as cell-based immunotherapies (24)(25)(26)(27)(28)(29)(30)(31)(32). However, clinical applications of DC-based therapies in autoimmune disease intervention are hampered by the concern that iDCs will develop into immunostimulatory cells upon encountering inflammatory stimuli in vivo.…”

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice

Ferreira

Gysemans

Demengeot

et al. 2014

The Journal of Immunology

112

View full text Add to dashboard Cite

The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is able to promote the generation of tolerogenic mature dendritic cells (mDCs) with an impaired ability to activate autoreactive T cells. These cells could represent a reliable tool for the promotion or restoration of Ag-specific tolerance through vaccination strategies, for example in type 1 diabetes patients. However, successful transfer of 1,25(OH)2D3-treated mDCs (1,25D3-mDCs) depends on the capacity of 1,25(OH)2D3 to imprint a similar tolerogenic profile in cells derived from diabetes-prone donors as from diabetes-resistant donors. In this study, we examined the impact of 1,25(OH)2D3 on the function and phenotype of mDCs originating from healthy (C57BL/6) and diabetes-prone (NOD) mice. We show that 1,25(OH)2D3 is able to imprint a phenotypic tolerogenic profile on DCs derived from both mouse strains. Both NOD- and C57BL/6-derived 1,25D3-mDCs decreased the proliferation and activation of autoreactive T cells in vitro, despite strain differences in the regulation of cytokine/chemokine expression. In addition, 1,25D3-mDCs from diabetes-prone mice expanded CD25+Foxp3+ regulatory T cells and induced intracellular IL-10 production by T cells in vitro. Furthermore, 1,25D3-mDCs exhibited an intact functional migratory capacity in vivo that favors homing to the liver and pancreas of adult NOD mice. More importantly, when cotransferred with activated CD4+ T cells into NOD.SCID recipients, 1,25D3-mDCs potently dampened the proliferation of autoreactive donor T cells in the pancreatic draining lymph nodes. Altogether, these results argue for the potential of 1,25D3-mDCs to restore Ag-specific immune tolerance and arrest autoimmune disease progression in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice

Ferreira

Gysemans

Demengeot

et al. 2014

The Journal of Immunology

112

View full text Add to dashboard Cite

show abstract

“…Current cancer treatments undergoing investigation include DCs loaded with tumor lysates [42] and genetically engineered DC vaccines expressing relevant tumour antigens [43]. Another approach for toleranceinducing therapies is the use of apoptotic cells as a "pool of antigens," which has the potential to induce a tolerogenic profile in DCs [44,45]. Induction of therapeutic tolerance in EAE has also been reported by targeting of DCs with monoclonal antibodies, such as anti-DEC205-mediated delivery of the PLP 139-151 [46], and also administration of splenocytes coupled with a myelin-peptide cocktail [47].…”

Section: Discussionmentioning

confidence: 99%

Stable antigen‐specific T‐cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients

et al. 2012

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease of the central nervous system. Current therapies decrease the frequency of relapses and limit, to some extent, but do not prevent disease progression. Hence, new therapeutic approaches that modify the natural course of MSneed to be identified. Tolerance induction to self‐antigens using monocyte‐derived dendritic cells (MDDCs) is a promising therapeutic strategy in autoimmunity. In this work, we sought to generate and characterize tolerogenic MDDCs (tolDCs) from relapsing‐remitting (RR) MSpatients, loaded with myelin peptides as specific antigen, with the aim of developing immunotherapeutics for MS. MDDCs were generated from both healthy‐blood donors and RR‐MSpatients, and MDDCmaturation was induced with a proinflammatory cytokine cocktail in the absence or presence of 1α,25‐dihydroxyvitamin‐D3, a tolerogenicity‐inducing agent. tolDCs were generated from monocytes of RR‐MSpatients as efficiently as from monocytes of healthy subjects. The RR‐MStolDCs expressed a stable semimature phenotype and an antiinflammatory profile as compared with untreated MDDCs. Importantly, myelin peptide‐loaded tolDCs induced stable antigen‐specific hyporesponsiveness in myelin‐reactive T cells from RR‐MS patients. These results suggest that myelin peptide‐loaded tolDCs may be a powerful tool for inducing myelin‐specific tolerance in RR‐MS patients.

show abstract

“…It was found that adoptive transfer of insulin peptide-pulsed, immature DCs could protect NOD mice from T1D whereas unpulsed DCs had no effect on T1D development (Haase et al, 2010). In another study, immature DCs derived from BM were pulsed with antigen-specific apoptotic bodies from the -cell line NIT-1 cells and the administration of these cells to NOD could decrease T1D incidence significantly and correlated positively with insulitis reduction (Marin-Gallen et al, 2010). All these results show that DC therapy is capable of preventing T1D in an antigen-specific manner in animal model and DCs expressing disease-associated antigens constitutes a promising strategy to prevent T1D.…”

Section: Exposure Of Therapeutic Dcs To Antigen Ex Vivomentioning

confidence: 99%

Autoantigen-Specific Immunotherapy

Han¹,

Donelan²,

Reeves³

et al. 2011

Type 1 Diabetes - Pathogenesis, Genetics and Immunotherapy

View full text Add to dashboard Cite

Dendritic cells pulsed with antigen-specific apoptotic bodies prevent experimental type 1 diabetes

Cited by 72 publications

References 30 publications

1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice

1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice

Stable antigen‐specific T‐cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients

Autoantigen-Specific Immunotherapy

Contact Info

Product

Resources

About