PMID- 16951385
OWN - NLM
STAT- MEDLINE
DCOM- 20061024
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 177
IP  - 6
DP  - 2006 Sep 15
TI  - Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary 
      progressive multiple sclerosis are activated and drive a proinflammatory immune 
      response.
PG  - 4196-202
AB  - Multiple sclerosis (MS) is postulated to be a T cell-mediated autoimmune disease 
      characterized clinically by a relapsing-remitting (RR) stage followed by a 
      secondary progressive (SP) phase. The progressive phase is felt to be secondary 
      to neuronal degenerative changes triggered by inflammation. The status of the 
      innate immune system and its relationship to the stages of MS is not well 
      understood. Dendritic cells (DCs) are professional APCs that are central cells of 
      the innate immune system and have the unique capacity to induce primary immune 
      responses. We investigated circulating myeloid DCs isolated directly from the 
      blood to determine whether there were abnormalities in myeloid DCs in MS and 
      whether they were related to disease stage. We found that SP-MS subjects had an 
      increased percentage of DCs expressing CD80, a decreased percentage expressing 
      PD-L1, and an increased percentage producing IL-12 and TNF-alpha compared with 
      RR-MS or controls. A higher percentage of DCs from both RR and SP-MS patients 
      expressed CD40 compared with controls. We then investigated the polarization 
      effect of DCs from MS patients on naive T cells taken from cord blood using a MLR 
      assay. Whereas DCs from RR-MS induced higher levels of Th1 (IFN-gamma, TNF-alpha) 
      and Th2 (IL-4, IL-13) cytokines compared with controls, DCs from SP-MS only 
      induced a polarized Th1 response. These results demonstrate abnormalities of DCs 
      in MS and may explain the immunologic basis for the different stages and clinical 
      patterns of MS.
FAU - Karni, Arnon
AU  - Karni A
AD  - Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical 
      School, Havard Medical School, Boston, MA 02115-5817, USA.
FAU - Abraham, Michal
AU  - Abraham M
FAU - Monsonego, Alon
AU  - Monsonego A
FAU - Cai, Guifang
AU  - Cai G
FAU - Freeman, Gordon J
AU  - Freeman GJ
FAU - Hafler, David
AU  - Hafler D
FAU - Khoury, Samia J
AU  - Khoury SJ
FAU - Weiner, Howard L
AU  - Weiner HL
LA  - eng
GR  - NS023132/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
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 (CD11c Antigen)
RN  - 0 (CD40 Antigens)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Adult
MH  - CD11c Antigen/biosynthesis
MH  - CD40 Antigens/biosynthesis/blood
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology/metabolism/*pathology
MH  - Female
MH  - Humans
MH  - *Immunity, Innate
MH  - Inflammation Mediators/blood/*metabolism
MH  - Interleukin-12/biosynthesis/blood
MH  - Leukocyte Count
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis, Chronic Progressive/*immunology/metabolism/*pathology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Up-Regulation/immunology
EDAT- 2006/09/05 09:00
MHDA- 2006/10/25 09:00
CRDT- 2006/09/05 09:00
PHST- 2006/09/05 09:00 [pubmed]
PHST- 2006/10/25 09:00 [medline]
PHST- 2006/09/05 09:00 [entrez]
AID - 177/6/4196 [pii]
AID - 10.4049/jimmunol.177.6.4196 [doi]
PST - ppublish
SO  - J Immunol. 2006 Sep 15;177(6):4196-202. doi: 10.4049/jimmunol.177.6.4196.