Abstract
Autoimmune pathologies are caused by a breakdown in self-tolerance. Tolerogenic dendritic cells (tolDC) are a promising immunotherapeutic tool for restoring self-tolerance in an antigen-specific manner. Studies about tolDC have focused largely on generating stable maturation-resistant DC, but few have fully addressed questions about the antigen-presenting and migratory capacities of these cells, prerequisites for successful immunotherapy. Here, we investigated whether human tolDC, generated with dexamethasone and the active form of vitamin D3, maintained their tolerogenic function upon activation with LPS (LPS-tolDC), while acquiring the ability to present exogenous autoantigen and to migrate in response to the CCR7 ligand CCL19. LPS activation led to important changes in the tolDC phenotype and function. LPS-tolDC, but not tolDC, expressed the chemokine receptor CCR7 and migrated in response to CCL19. Furthermore, LPS-tolDC were superior to tolDC in their ability to present type II collagen, a candidate autoantigen in rheumatoid arthritis. tolDC and LPS-tolDC had low stimulatory capacity for allogeneic, naive T cells and skewed T cell polarization toward an anti-inflammatory phenotype, although LPS-tolDC induced significantly higher levels of IL-10 production by T cells. Our finding that LPS activation is essential for inducing migratory and antigen-presenting activity in tolDC is important for optimizing their therapeutic potential. J. Leukoc. Biol. 85: 243-250; 2009.
| Original language | English |
|---|---|
| Pages (from-to) | 243-250 |
| Number of pages | 8 |
| Journal | Journal of Leukocyte Biology |
| Volume | 85 |
| Issue number | 2 |
| Early online date | 6 Nov 2008 |
| DOIs | |
| Publication status | Published - 1 Feb 2009 |
Keywords
- tolerance
- migration
- CCR7
- naive T cells
- immunotherapy
- cardiac allograft survival
- collagen-induced arthritis
- regulatory T-cells
- immune deviaton
- in-vivo
- inflammatory stimuli
- RNA interference
- express IL-4
- II collagen
- tolerance
- migration
- CCR7
- naïve T cells
Cite this
LPS activation is required for migratory activity and antigen presentation by tolerogenic dendritic cells. / Musculoskeletal Research Group.
In: Journal of Leukocyte Biology, Vol. 85, No. 2, 01.02.2009, p. 243-250.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - LPS activation is required for migratory activity and antigen presentation by tolerogenic dendritic cells
AU - Anderson, Amy Nancy
AU - Swan, David J
AU - Sayers, Bethan L.
AU - Harry, Rachel A.
AU - Patterson, Angela Margaret
AU - von Delwig, Alexei
AU - Robinson, J.
AU - Isaacs, John D.
AU - Hilkens, Catharien M. U.
AU - Musculoskeletal Research Group
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Autoimmune pathologies are caused by a breakdown in self-tolerance. Tolerogenic dendritic cells (tolDC) are a promising immunotherapeutic tool for restoring self-tolerance in an antigen-specific manner. Studies about tolDC have focused largely on generating stable maturation-resistant DC, but few have fully addressed questions about the antigen-presenting and migratory capacities of these cells, prerequisites for successful immunotherapy. Here, we investigated whether human tolDC, generated with dexamethasone and the active form of vitamin D3, maintained their tolerogenic function upon activation with LPS (LPS-tolDC), while acquiring the ability to present exogenous autoantigen and to migrate in response to the CCR7 ligand CCL19. LPS activation led to important changes in the tolDC phenotype and function. LPS-tolDC, but not tolDC, expressed the chemokine receptor CCR7 and migrated in response to CCL19. Furthermore, LPS-tolDC were superior to tolDC in their ability to present type II collagen, a candidate autoantigen in rheumatoid arthritis. tolDC and LPS-tolDC had low stimulatory capacity for allogeneic, naive T cells and skewed T cell polarization toward an anti-inflammatory phenotype, although LPS-tolDC induced significantly higher levels of IL-10 production by T cells. Our finding that LPS activation is essential for inducing migratory and antigen-presenting activity in tolDC is important for optimizing their therapeutic potential. J. Leukoc. Biol. 85: 243-250; 2009.
AB - Autoimmune pathologies are caused by a breakdown in self-tolerance. Tolerogenic dendritic cells (tolDC) are a promising immunotherapeutic tool for restoring self-tolerance in an antigen-specific manner. Studies about tolDC have focused largely on generating stable maturation-resistant DC, but few have fully addressed questions about the antigen-presenting and migratory capacities of these cells, prerequisites for successful immunotherapy. Here, we investigated whether human tolDC, generated with dexamethasone and the active form of vitamin D3, maintained their tolerogenic function upon activation with LPS (LPS-tolDC), while acquiring the ability to present exogenous autoantigen and to migrate in response to the CCR7 ligand CCL19. LPS activation led to important changes in the tolDC phenotype and function. LPS-tolDC, but not tolDC, expressed the chemokine receptor CCR7 and migrated in response to CCL19. Furthermore, LPS-tolDC were superior to tolDC in their ability to present type II collagen, a candidate autoantigen in rheumatoid arthritis. tolDC and LPS-tolDC had low stimulatory capacity for allogeneic, naive T cells and skewed T cell polarization toward an anti-inflammatory phenotype, although LPS-tolDC induced significantly higher levels of IL-10 production by T cells. Our finding that LPS activation is essential for inducing migratory and antigen-presenting activity in tolDC is important for optimizing their therapeutic potential. J. Leukoc. Biol. 85: 243-250; 2009.
KW - tolerance
KW - migration
KW - CCR7
KW - naive T cells
KW - immunotherapy
KW - cardiac allograft survival
KW - collagen-induced arthritis
KW - regulatory T-cells
KW - immune deviaton
KW - in-vivo
KW - inflammatory stimuli
KW - RNA interference
KW - express IL-4
KW - II collagen
KW - tolerance
KW - migration
KW - CCR7
KW - naïve T cells
U2 - 10.1189/jlb.0608374
DO - 10.1189/jlb.0608374
M3 - Article
VL - 85
SP - 243
EP - 250
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 2
ER -