PMID- 22355103
OWN - NLM
STAT- MEDLINE
DCOM- 20120504
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 10
DP  - 2012 Mar 6
TI  - CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis 
      by regulating GM-CSF and IL-23 production in dendritic cells.
PG  - 3897-902
LID - 10.1073/pnas.1114153109 [doi]
AB  - Dendritic cells (DCs) are pivotal for the development of experimental autoimmune 
      encephalomyelitis (EAE). However, the mechanisms by which they control disease 
      remain to be determined. This study demonstrates that expression of CC chemokine 
      receptor 4 (CCR4) by DCs is required for EAE induction. CCR4(-/-) mice presented 
      enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF 
      expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or 
      intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored 
      EAE in CCR4(-/-) mice, indicating that CCR4(+) DCs are cellular mediators of EAE 
      development. Mechanistically, CCR4(-/-) DCs were less efficient in GM-CSF and 
      IL-23 production and also T(H)-17 maintenance. Intraspinal IL-23 reconstitution 
      restored EAE in CCR4(-/-) mice, whereas intracerebral inoculation using 
      IL-23(-/-) DCs or GM-CSF(-/-) DCs failed to induce disease. Thus, CCR4-dependent 
      GM-CSF production in DCs required for IL-23 release in these cells is a major 
      component in the development of EAE. Our study identified a unique role for CCR4 
      in regulating DC function in EAE, harboring therapeutic potential for the 
      treatment of CNS autoimmunity by targeting CCR4 on this specific cell type.
FAU - Poppensieker, Karola
AU  - Poppensieker K
AD  - Institute of Molecular Psychiatry, University of Bonn, 53127 Bonn, Germany.
FAU - Otte, David-Marian
AU  - Otte DM
FAU - Schurmann, Britta
AU  - Schurmann B
FAU - Limmer, Andreas
AU  - Limmer A
FAU - Dresing, Philipp
AU  - Dresing P
FAU - Drews, Eva
AU  - Drews E
FAU - Schumak, Beatrix
AU  - Schumak B
FAU - Klotz, Luisa
AU  - Klotz L
FAU - Raasch, Jennifer
AU  - Raasch J
FAU - Mildner, Alexander
AU  - Mildner A
FAU - Waisman, Ari
AU  - Waisman A
FAU - Scheu, Stefanie
AU  - Scheu S
FAU - Knolle, Percy
AU  - Knolle P
FAU - Forster, Irmgard
AU  - Forster I
FAU - Prinz, Marco
AU  - Prinz M
FAU - Maier, Wolfgang
AU  - Maier W
FAU - Zimmer, Andreas
AU  - Zimmer A
FAU - Alferink, Judith
AU  - Alferink J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120221
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Ccr4 protein, mouse)
RN  - 0 (Interleukin-23)
RN  - 0 (Ligands)
RN  - 0 (Receptors, CCR4)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
CIN - Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):E2412-3; author reply E2414. PMID: 
      22864916
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Dendritic Cells/*cytology
MH  - Encephalomyelitis, Autoimmune, Experimental/*immunology/metabolism
MH  - *Gene Expression Regulation
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*metabolism
MH  - Inflammation
MH  - Interleukin-23/*metabolism
MH  - Ligands
MH  - Macrophages/cytology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Models, Biological
MH  - Receptors, CCR4/metabolism/*physiology
PMC - PMC3309768
COIS- The authors declare no conflict of interest.
EDAT- 2012/02/23 06:00
MHDA- 2012/05/05 06:00
PMCR- 2012/09/06
CRDT- 2012/02/23 06:00
PHST- 2012/02/23 06:00 [entrez]
PHST- 2012/02/23 06:00 [pubmed]
PHST- 2012/05/05 06:00 [medline]
PHST- 2012/09/06 00:00 [pmc-release]
AID - 1114153109 [pii]
AID - 201114153 [pii]
AID - 10.1073/pnas.1114153109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3897-902. doi: 
      10.1073/pnas.1114153109. Epub 2012 Feb 21.