PMID- 18754812
OWN - NLM
STAT- MEDLINE
DCOM- 20090220
LR  - 20211020
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 126
IP  - 1
DP  - 2009 Jan
TI  - Dendritic cells modulated by innate immunity improve collagen-induced arthritis 
      and induce regulatory T cells in vivo.
PG  - 35-44
LID - 10.1111/j.1365-2567.2008.02875.x [doi]
AB  - Dendritic cells (DCs) mediate interactions between innate and specific immunity 
      and may induce regulatory mechanisms. We investigated the effects of modulated 
      DCs in mice with collagen-induced arthritis (CIA) and tested the responses of 
      cells to induced naturally occurring regulatory T cells. DCs were stimulated or 
      not with DNA or lipopolysaccharide (LPS) for 24 hr. DC maturation was assayed, 
      and then modulated DCs were intraperitoneally injected on day 14 into DBA/1 mice 
      to treat CIA. In addition to arthritis scores and type 2 collagen (CII) response, 
      the induction of CD4(+) CD25(+) T cells was analysed by flow cytometry in 
      peripheral blood and the expression of Foxp3, transforming growth factor 
      (TGF)-beta, interleukin (IL)-10 and cytotoxic T-lymphocyte antigen (CTLA)-4 was 
      quantified. Finally, the expression of indoleamine-2,3-dioxygenase (IDO) was 
      assayed in DCs. In comparison with LPS-stimulated DCs, plasmid-stimulated DCs 
      expressed lower levels of major histocompatibility complex (MHC) class II, CD40, 
      CD80 and CD86 molecules and secreted less IL-12p70, interferon (IFN)-gamma, IL-10 
      and TNF-alpha, displaying a semi-mature phenotype. Compared with non-stimulated 
      DCs, stimulated DCs improved arthritis scores when injected after immunization, 
      without modifying the T helper type 1 (Th1)/Th2 balance of the immune response 
      against collagen. Stimulated DCs induced markers for regulatory T cells (Foxp3, 
      TGF-beta1 and CTLA-4) in vivo. Only LPS-stimulated DCs expressed IDO, which may 
      explain their better therapeutic efficacy. Regulatory mechanisms were induced 
      using DCs modulated by innate immunity stimulators. Innate immunity mechanisms do 
      not require the presence of the disease-causing antigen, even in T- and B-cell 
      specific diseases. Our results have implications for the treatment of rheumatoid 
      arthritis, an autoimmune disease whose triggering antigen has not been 
      identified, and substantially clarify the role of regulatory T cells in CIA.
FAU - Jaen, Olivier
AU  - Jaen O
AD  - INSERM ERI18, Paris 13 University, AP-HP Rheumatology Department, Avicenne 
      Hospital, Bobigny, France.
FAU - Rulle, Sandrine
AU  - Rulle S
FAU - Bessis, Natacha
AU  - Bessis N
FAU - Zago, Abokouo
AU  - Zago A
FAU - Boissier, Marie-Christophe
AU  - Boissier MC
FAU - Falgarone, Geraldine
AU  - Falgarone G
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080827
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Collagen Type II)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/immunology/*prevention & control
MH  - Cell Differentiation/immunology
MH  - Collagen Type II/immunology
MH  - Dendritic Cells/immunology/*transplantation
MH  - Forkhead Transcription Factors/biosynthesis
MH  - Immune Tolerance
MH  - Immunity, Innate
MH  - Immunoglobulin G/biosynthesis
MH  - Interleukin-10/biosynthesis
MH  - Lipopolysaccharides/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Plasmids/immunology
MH  - Polymerase Chain Reaction/methods
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - Th2 Cells/immunology
MH  - Transforming Growth Factor beta1/biosynthesis
PMC - PMC2632710
EDAT- 2008/08/30 09:00
MHDA- 2009/02/21 09:00
PMCR- 2010/01/01
CRDT- 2008/08/30 09:00
PHST- 2008/08/30 09:00 [pubmed]
PHST- 2009/02/21 09:00 [medline]
PHST- 2008/08/30 09:00 [entrez]
PHST- 2010/01/01 00:00 [pmc-release]
AID - IMM2875 [pii]
AID - 10.1111/j.1365-2567.2008.02875.x [doi]
PST - ppublish
SO  - Immunology. 2009 Jan;126(1):35-44. doi: 10.1111/j.1365-2567.2008.02875.x. Epub 
      2008 Aug 27.