PMID- 19040426
OWN - NLM
STAT- MEDLINE
DCOM- 20100125
LR  - 20211020
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 128
IP  - 1 Suppl
DP  - 2009 Sep
TI  - The role of dendritic cells in the mechanism of action of a peptide that 
      ameliorates lupus in murine models.
PG  - e395-405
LID - 10.1111/j.1365-2567.2008.02988.x [doi]
AB  - Systemic lupus erythematosus (SLE) is characterized in its early stages by the 
      expansion of autoreactive T cells that trigger B-cell activation with subsequent 
      multi-organ injury. Dendritic cells (DCs) in lupus were found to display an 
      aberrant phenotype with higher expression of the maturation markers major 
      histocompatibility complex (MHC) class II, CD80 and CD86, as well as higher 
      production of proinflammatory cytokines including interleukin-12 (IL-12), 
      resulting in an increased ability to activate T cells. A peptide (hCDR1) based on 
      the complementarity determining region-1 of an anti-DNA antibody ameliorated SLE 
      in both induced and spontaneous lupus models by downregulating T-cell functions. 
      Our objectives were to determine whether DCs play a role in promoting the 
      beneficial effects of hCDR1. We showed here that treatment with hCDR1 lowered the 
      expression levels of MHC class II, CD80 and CD86 on DCs. The latter effect was 
      associated with downregulation of messenger RNA expression and secretion of 
      IL-12, a cytokine that upregulated T-cell proliferation and interferon-gamma 
      (IFN-gamma) secretion. Moreover, DCs derived from hCDR1-treated mice 
      downregulated proliferation and IFN-gamma secretion by T cells from untreated 
      mice. Upregulation of transforming growth factor-beta (TGF-beta) secretion by T 
      cells, following treatment with hCDR1, resulted in downregulation of IFN-gamma 
      production and contributed to the phenotypic changes and magnitude of IL-12 
      secretion by DCs. The ameliorating effects of hCDR1 are therefore mediated at 
      least partially by the upregulated secretion of TGF-beta by T cells that 
      contribute to the induction of DCs with immature phenotype and suppressed 
      functions. The resulting DCs further downregulate autoreactive T-cell functions.
FAU - Sela, Uri
AU  - Sela U
AD  - Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
FAU - Sharabi, Amir
AU  - Sharabi A
FAU - Dayan, Molly
AU  - Dayan M
FAU - Hershkoviz, Rami
AU  - Hershkoviz R
FAU - Mozes, Edna
AU  - Mozes E
LA  - eng
PT  - Journal Article
DEP - 20081124
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Autoantigens)
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CDR1 protein, human)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Peptides)
RN  - 0 (Transforming Growth Factor beta)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Autoantigens/pharmacology/*therapeutic use
MH  - B7-1 Antigen/drug effects/immunology
MH  - B7-2 Antigen/drug effects/immunology
MH  - Dendritic Cells/drug effects/*immunology
MH  - Down-Regulation
MH  - Female
MH  - Histocompatibility Antigens Class II/drug effects/*immunology
MH  - Humans
MH  - Interferon-gamma/agonists/immunology/metabolism
MH  - Interleukin-12/antagonists & inhibitors/immunology/pharmacology
MH  - Lupus Erythematosus, Systemic/*drug therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nerve Tissue Proteins/pharmacology/*therapeutic use
MH  - Peptides/pharmacology/therapeutic use
MH  - T-Lymphocytes/drug effects/immunology
MH  - Transforming Growth Factor beta/pharmacology
MH  - Up-Regulation
PMC - PMC2753948
EDAT- 2008/12/02 09:00
MHDA- 2010/01/26 06:00
PMCR- 2010/09/01
CRDT- 2008/12/02 09:00
PHST- 2008/12/02 09:00 [pubmed]
PHST- 2010/01/26 06:00 [medline]
PHST- 2008/12/02 09:00 [entrez]
PHST- 2010/09/01 00:00 [pmc-release]
AID - IMM2988 [pii]
AID - 10.1111/j.1365-2567.2008.02988.x [doi]
PST - ppublish
SO  - Immunology. 2009 Sep;128(1 Suppl):e395-405. doi: 
      10.1111/j.1365-2567.2008.02988.x. Epub 2008 Nov 24.