TY - JOUR
T1 - Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis
AU - Cudrici, Cornelia
AU - Ito, Takahiro
AU - Zafranskaia, Ekaterina
AU - Niculescu, Florin
AU - Mullen, Katherine M.
AU - Vlaicu, Sonia
AU - Judge, Susan I.V.
AU - Calabresi, Peter A.
AU - Rus, Horea
N1 - Funding Information:
This work was supported by US Public Health Grant NS 42011 (HR), NS041435 (PAC) and by National Multiple Sclerosis Society PP0997 (SIVJ), the Veteran's Administration Maryland Health Care System, MS Center of Excellence, Baltimore MD (HR and SIVJ).
PY - 2007/10
Y1 - 2007/10
N2 - We have analyzed the localization of dendritic cells (DCs) in non-lesional gray matter (NLGM) in comparison to non-lesional white matter (NLWM) and acute or chronic active multiple sclerosis (MS) lesions. Immunohistochemistry was performed on cryostat sections for DCs markers (CD209, CD205, CD83) and other markers for inflammatory cells (CD68, CD8, CD4, CD3, CCR7, CCR5). We found cells expressing CD209 and containing myelin basic protein in both perivascular and parenchymal areas of NLGM. Our findings showing the expression of CD209+ cells in NLGM parenchymal areas are surprising relative to the previous literature which reported the presence of CD209+ DCs only in MS plaque perivascular areas. Although less numerous than CD209+ cells, NLGM cells expressing mature DCs marker CD205 were consistently detected in perivascular cuffs of most lesions. In double labeling experiments, some but not all of the CD209+ cells also expressed CD68 and CCR5. We also found CD209+ cells in close contact with CD3+ lymphocytes suggesting that DCs might contribute to the local activation of pathogenic T cells in the NLGM. Since injury to the NLGM is one of the key factors associated with disability accumulation, targeting DCs may represent a possible new therapeutic approach in MS to prevent disease progression.
AB - We have analyzed the localization of dendritic cells (DCs) in non-lesional gray matter (NLGM) in comparison to non-lesional white matter (NLWM) and acute or chronic active multiple sclerosis (MS) lesions. Immunohistochemistry was performed on cryostat sections for DCs markers (CD209, CD205, CD83) and other markers for inflammatory cells (CD68, CD8, CD4, CD3, CCR7, CCR5). We found cells expressing CD209 and containing myelin basic protein in both perivascular and parenchymal areas of NLGM. Our findings showing the expression of CD209+ cells in NLGM parenchymal areas are surprising relative to the previous literature which reported the presence of CD209+ DCs only in MS plaque perivascular areas. Although less numerous than CD209+ cells, NLGM cells expressing mature DCs marker CD205 were consistently detected in perivascular cuffs of most lesions. In double labeling experiments, some but not all of the CD209+ cells also expressed CD68 and CCR5. We also found CD209+ cells in close contact with CD3+ lymphocytes suggesting that DCs might contribute to the local activation of pathogenic T cells in the NLGM. Since injury to the NLGM is one of the key factors associated with disability accumulation, targeting DCs may represent a possible new therapeutic approach in MS to prevent disease progression.
KW - Dendritic cells
KW - Macrophages
KW - Multiple sclerosis
KW - Non-lesional gray matter
KW - T lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=34548250519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548250519&partnerID=8YFLogxK
U2 - 10.1016/j.yexmp.2007.05.006
DO - 10.1016/j.yexmp.2007.05.006
M3 - Article
C2 - 17662270
AN - SCOPUS:34548250519
SN - 0014-4800
VL - 83
SP - 198
EP - 206
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 2
ER -