Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors.
BACKGROUND
The role of the adaptive immune system and more specifically T cells in the pathogenesis of multiple sclerosis (MS) has been studied extensively. Emerging evidence suggests that dendritic cells (DCs), which are innate immune cells, also contribute to MS.


OBJECTIVE
This study aimed to characterize circulating DC populations in MS and to investigate the contribution of MS-associated genetic risk factors to DCs.


METHODS
Ex vivo analysis of conventional (cDCs) and plasmacytoid DCs (pDCs) was carried out on peripheral blood of MS patients (n = 110) and age- and gender-matched healthy controls (n = 112).


RESULTS
Circulating pDCs were significantly decreased in patients with chronic progressive MS compared to relapsing-remitting MS and healthy controls. While no differences in cDCs frequency were found between the different study groups, HLA-DRB1*1501(+) MS patients and patients not carrying the protective IL-7Rα haplotype 2 have reduced frequencies of circulating cDCs and pDCs, respectively. MS-derived DCs showed enhanced IL-12p70 production upon TLR ligation and had an increased expression of the migratory molecules CCR5 and CCR7 as well as an enhanced in vitro chemotaxis.


CONCLUSIONS
DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.
Biomedical Research Institute, Hasselt University, Belgium.
Kristof
K
Thewissen
Amber H
AH
Nuyts
Nathalie
N
Deckx
Bart
B
Van Wijmeersch
Guy
G
Nagels
Marie
M
D'hooghe
Barbara
B
Willekens
Patrick
P
Cras
Bert O
BO
Eijnde
Herman
H
Goossens
Viggo F I
VF
Van Tendeloo
Piet
P
Stinissen
Zwi N
ZN
Berneman
Niels
N
Hellings
Nathalie
N
Cools
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D002633:Chemotaxis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics* / Q000276:immunology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics* / Q000276:immunology*; D010641:Phenotype; D019713:Receptors, CCR5 / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000235:genetics; D012307:Risk Factors; D051193:Toll-Like Receptors / Q000378:metabolism; D055815:Young Adult
C584933:CCR5 protein, human; C515370:CCR7 protein, human; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; C109985:IL17RA protein, human; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D053722:Receptors, Interleukin-17; D051193:Toll-Like Receptors
Dendritic cells; MS-associated genetic risk factors; costimulatory molecules; migration; multiple sclerosis