PMID- 24218453
OWN - NLM
STAT- MEDLINE
DCOM- 20140218
LR  - 20231213
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 191
IP  - 12
DP  - 2013 Dec 15
TI  - Antigen-specific induced T regulatory cells impair dendritic cell function via an 
      IL-10/MARCH1-dependent mechanism.
PG  - 5875-84
LID - 10.4049/jimmunol.1301693 [doi]
AB  - Foxp3(+) T regulatory cells (Tregs) are critically important for the maintenance 
      of immunological tolerance, immune homeostasis, and prevention of autoimmunity. 
      Dendritic cells (DCs) are one of the major targets of Treg-mediated suppression. 
      Some studies have suggested that Treg-mediated suppression of DC function is 
      mediated by the interaction of CTLA-4 on Tregs with CD80/CD86 on the DCs 
      resulting in downregulation of CD80/CD86 expression and a decrease in 
      costimulation. We have re-examined the effects of Tregs on mouse DC function in a 
      model in which Ag-specific, induced Tregs (iTregs) are cocultured with DCs in the 
      absence of T effector cells. iTreg-treated DCs are markedly defective in their 
      capacity to activate naive T cells. iTregs from CTLA-4-deficient mice failed to 
      induce downregulation of CD80/CD86, but DCs treated with CTLA-4-deficient iTregs 
      still exhibited impaired capacity to activate naive T cells. The iTreg-induced 
      defect in DC function could be completely reversed by anti-IL-10, and 
      IL-10-deficient iTregs failed to downregulate DC function. iTreg-treated DCs 
      expressed high levels of MARCH1, an E3 ubiquitin ligase, recently found to 
      degrade CD86 and MHC class II on the DCs and expressed lower levels of CD83, a 
      molecule involved in neutralizing the function of MARCH1. Both the enhanced 
      expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 
      produced by the iTregs. Taken together, these studies demonstrate that a major 
      suppressive mechanism of DC function by iTregs is secondary to the effects of 
      IL-10 on MARCH1 and CD83 expression.
FAU - Chattopadhyay, Gouri
AU  - Chattopadhyay G
AD  - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, 
      National Institutes of Health, Bethesda, MD 20892.
FAU - Shevach, Ethan M
AU  - Shevach EM
LA  - eng
GR  - Z01 AI000224-27/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20131111
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Ctla4 protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (IL10 protein, mouse)
RN  - 0 (Immunoglobulins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Rag2 protein, mouse)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.3.2.27 (MARCH1 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Antigens, CD/biosynthesis/genetics/*physiology
MH  - B7-1 Antigen/biosynthesis/genetics
MH  - B7-2 Antigen/biosynthesis/genetics
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CTLA-4 Antigen/deficiency/physiology
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - DNA-Binding Proteins/deficiency
MH  - Dendritic Cells/*immunology
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Flow Cytometry
MH  - Gene Expression Regulation/*immunology
MH  - Histocompatibility Antigens Class II/immunology
MH  - Immune Tolerance/*immunology
MH  - Immunoglobulins/biosynthesis/genetics/*physiology
MH  - Interleukin-10/antagonists & inhibitors/deficiency/metabolism/*physiology
MH  - Lymphocyte Activation
MH  - Membrane Glycoproteins/biosynthesis/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - RNA, Messenger/biosynthesis
MH  - *T-Cell Antigen Receptor Specificity
MH  - T-Lymphocytes, Regulatory/*immunology/metabolism
MH  - Ubiquitin-Protein Ligases/biosynthesis/genetics/*physiology
MH  - CD83 Antigen
PMC - PMC3858537
MID - NIHMS529610
EDAT- 2013/11/13 06:00
MHDA- 2014/02/19 06:00
PMCR- 2014/12/15
CRDT- 2013/11/13 06:00
PHST- 2013/11/13 06:00 [entrez]
PHST- 2013/11/13 06:00 [pubmed]
PHST- 2014/02/19 06:00 [medline]
PHST- 2014/12/15 00:00 [pmc-release]
AID - jimmunol.1301693 [pii]
AID - 10.4049/jimmunol.1301693 [doi]
PST - ppublish
SO  - J Immunol. 2013 Dec 15;191(12):5875-84. doi: 10.4049/jimmunol.1301693. Epub 2013 
      Nov 11.