Stem cells ameliorate EAE via an indoleamine 2,3-dioxygenase (IDO) mechanism.
Syngeneic, pluripotent Lin(-)Sca1(+) bone marrow stem cells (SC), transferred to mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis, enhanced recovery, prevented relapses and promoted myelin repair. SC-treated mice showed elevated interferon-gamma production and induction of indoleamine 2,3-dioxygenase (IDO) in CD11c(+) dendritic cells (DC). IDO induction was specific since in the presence of IDO-producing CD11c(+) DC, PLP stimulated T cell proliferation was inhibited and the IDO-inhibitor, 1-MT, abrogated the SC effect. Relapse prevention during chronic disease correlated with decreased responsiveness to PLP(178-191) and MBP(85-99). Thus, pluripotent SC induce IDO in DC leading to inhibition of antigen reactivity and spreading in EAE.
Matysiak
Mariola
M
Department of Neurology, Medical University of Lodz, Lodz, Poland.
Stasiołek
Mariusz
M
Orłowski
Wojciech
W
Jurewicz
Anna
A
Janczar
Szymon
S
Raine
Cedric S
CS
Selmaj
Krzysztof
K
D000818:Animals; D017209:Apoptosis; D000067696:Ataxin-1; D000067528:Ataxins; D001921:Brain / Q000473:pathology; D039521:CD11c Antigen / Q000032:analysis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D005260:Female; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D010446:Peptide Fragments / Q000276:immunology; D033581:Stem Cell Transplantation; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D039521:CD11c Antigen; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D007371:Interferon-gamma