PMID- 18981105
OWN - NLM
STAT- MEDLINE
DCOM- 20081212
LR  - 20190516
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 181
IP  - 10
DP  - 2008 Nov 15
TI  - Dendritic cell differentiation induced by a self-peptide derived from 
      apolipoprotein E.
PG  - 6859-71
AB  - Dendritic cells (DCs) are professional APCs and potent stimulators of naive T 
      cells. Since DCs have the ability to immunize or tolerize T cells they are unique 
      candidates for use in immunotherapy. Our laboratory has discovered that a 
      naturally processed self-peptide from apolipoprotein E, Ep1.B, induces DC-like 
      morphology and surface marker expression in a murine monocytic cell line 
      (PU5-1.8), human monocytic cell line (U937), murine splenocytes, and human 
      peripheral blood monocytes. Microscopy and flow cytometric analysis revealed that 
      Ep1.B-treated cells display decreased adherence to plastic and increased 
      aggregation, dendritic processes, and expression of DC surface markers, including 
      DEC-205, CD11c, B7.1, and B7.2. These effects were observed in both PU5-1.8 cells 
      and splenocytes from various mouse strains including BALB/c, C57BL/6, NOD/Lt, and 
      C3H/HeJ. Coadministration of Ep1.B with OVA antigenic peptide functions in 
      dampening specific immune response to OVA. Ep1.B down-regulates proliferation of 
      T cells and IFN-gamma production and stimulates IL-10 secretion in immunized 
      mice. Ep1.B-induced differentiation resulted in the activation of PI3K and MAPK 
      signaling pathways, including ERK1/2, p38, and JNK. We also found that NF-kappaB, 
      a transcription factor essential for DC differentiation, is critical in mediating 
      the effects of Ep1.B. Ep1.B-induced differentiation is independent of 
      MyD88-dependent pathway of TLR signaling. Cumulatively, these findings suggest 
      that Ep1.B acts by initiating a signal transduction cascade in monocytes leading 
      to their differentiation into DCs.
FAU - Stephens, Tracey A
AU  - Stephens TA
AD  - Department of Microbiology and Immunology, University of Western Ontario, London, 
      Ontario, Canada.
FAU - Nikoopour, Enayat
AU  - Nikoopour E
FAU - Rider, Beverly J
AU  - Rider BJ
FAU - Leon-Ponte, Matilde
AU  - Leon-Ponte M
FAU - Chau, Thu A
AU  - Chau TA
FAU - Mikolajczak, Sebastian
AU  - Mikolajczak S
FAU - Chaturvedi, Pratibha
AU  - Chaturvedi P
FAU - Lee-Chan, Edwin
AU  - Lee-Chan E
FAU - Flavell, Richard A
AU  - Flavell RA
FAU - Haeryfar, S M Mansour
AU  - Haeryfar SM
FAU - Madrenas, Joaquin
AU  - Madrenas J
FAU - Singh, Bhagirath
AU  - Singh B
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Apolipoproteins E)
RN  - 0 (Peptide Fragments)
RN  - 0 (apolipoprotein E (239-252), mouse)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/*immunology
MH  - Blotting, Western
MH  - Cell Adhesion/immunology
MH  - Cell Differentiation/*immunology
MH  - Cell Line
MH  - Dendritic Cells/*cytology/immunology
MH  - Flow Cytometry
MH  - Humans
MH  - Lymphocyte Activation/immunology
MH  - Lymphocyte Culture Test, Mixed
MH  - Mice
MH  - Peptide Fragments/*immunology
MH  - Signal Transduction/*immunology
MH  - T-Lymphocytes/immunology
EDAT- 2008/11/05 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/11/05 09:00
PHST- 2008/11/05 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/11/05 09:00 [entrez]
AID - 181/10/6859 [pii]
AID - 10.4049/jimmunol.181.10.6859 [doi]
PST - ppublish
SO  - J Immunol. 2008 Nov 15;181(10):6859-71. doi: 10.4049/jimmunol.181.10.6859.