PMID- 20039433
OWN - NLM
STAT- MEDLINE
DCOM- 20100311
LR  - 20151119
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 62
IP  - 1
DP  - 2010 Jan
TI  - Novel role of plasmacytoid dendritic cells in humans: induction of 
      interleukin-10-producing Treg cells by plasmacytoid dendritic cells in patients 
      with rheumatoid arthritis responding to therapy.
PG  - 53-63
LID - 10.1002/art.25037 [doi]
AB  - OBJECTIVE: Reestablishing immune tolerance and long-term suppression of disease 
      represent major therapeutic goals in rheumatoid arthritis (RA). Dendritic cells 
      (DCs) likely play a central role in such regulation via the expansion and/or 
      induction of Treg cells. The present study was undertaken to explore the 
      contribution of DCs to the development of Treg cells in a human autoimmune 
      disease setting. METHODS: DC subsets were characterized by flow cytometry in the 
      peripheral blood and synovial fluid of patients with RA. Proliferation of and 
      cytokine release by naive CD4+CD25- T cells were measured in cocultures of these 
      cells with DCs from patients with RA and healthy controls. The suppressive 
      capacity of DC-polarized T cells was explored in vitro by a standard suppression 
      assay. RESULTS: Only very low numbers of both plasmacytoid DCs (CD303+) and 
      myeloid DCs (CD1c+) were present in the peripheral blood of patients with active 
      RA. In contrast, patients with therapy-induced remission of RA exhibited higher 
      numbers of circulating plasmacytoid DCs. Mature plasmacytoid DCs from RA patients 
      with low disease activity, but not those from healthy controls, expressed high 
      levels of indoleamine 2,3-dioxygenase and promoted the differentiation of 
      allogeneic naive CD4+CD25- T cells into interleukin-10-secreting Treg cells, or 
      Tr1 cells, that showed poor proliferation in vitro. Importantly, these 
      plasmacytoid DC-primed Treg cells potently suppressed the proliferation of 
      autologous naive CD4+ T cells, in a dose-dependent manner. CONCLUSION: These 
      results demonstrate, for the first time, that human plasmacytoid DCs may be 
      educated within the rheumatoid microenvironment to acquire a tolerogenic 
      phenotype. Modulation of the immune response by plasmacytoid DCs might provide 
      novel immune-based therapies in autoimmunity and transplantation.
FAU - Kavousanaki, Melina
AU  - Kavousanaki M
AD  - University of Crete, Crete, Greece.
FAU - Makrigiannakis, Antonis
AU  - Makrigiannakis A
FAU - Boumpas, Dimitrios
AU  - Boumpas D
FAU - Verginis, Panayotis
AU  - Verginis P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 130068-27-8 (Interleukin-10)
RN  - B72HH48FLU (Infliximab)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Antigens, CD/metabolism
MH  - Antirheumatic Agents/therapeutic use
MH  - Arthritis, Rheumatoid/drug therapy/*immunology/physiopathology
MH  - Cell Count
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immune Tolerance/*immunology
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism
MH  - Infliximab
MH  - Interleukin-10/metabolism
MH  - Male
MH  - Methotrexate/therapeutic use
MH  - Middle Aged
MH  - Plasma Cells/*immunology
MH  - T-Lymphocytes, Regulatory/cytology/immunology
EDAT- 2009/12/30 06:00
MHDA- 2010/03/12 06:00
CRDT- 2009/12/30 06:00
PHST- 2009/12/30 06:00 [entrez]
PHST- 2009/12/30 06:00 [pubmed]
PHST- 2010/03/12 06:00 [medline]
AID - 10.1002/art.25037 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2010 Jan;62(1):53-63. doi: 10.1002/art.25037.