A novel model of demyelinating encephalomyelitis induced by monocytes and dendritic cells.
Local inflammation may be a precipitating event in autoimmune processes. In this study, we demonstrate that regulated influx of monocytes and dendritic cells (DC) into the CNS causes an acute neurological syndrome that results in a demyelinating encephalomyelitis. Expansion of monocytes and DC by conditional expression of Flt3 ligand in animals expressing CCL2 in the CNS promoted parenchymal cell infiltration and ascending paralysis in 100% of the mice within 9 days of Flt3 ligand induction. Depletion of circulating monocytes and DC reduced disease incidence and severity. Unlike the classical models of experimental autoimmune encephalomyelitis, depletion of CD4+ and CD8+ T cells did not affect disease induction. T cells and demyelinating lesions were observed in the CNS at a later stage as a result of organ-specific inflammation. We propose that alterations in the numbers or function of monocytes and DC coupled to dysregulated expression of chemokines in the neural tissues, favors development of CNS autoimmune disease.
Furtado
Glaucia C
GC
Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029-6574, USA. glaucia.furtado@mssm.edu
Piña
Beatrice
B
Tacke
Frank
F
Gaupp
Stefanie
S
van Rooijen
Nico
N
Moran
Thomas M
TM
Randolph
Gwendalyn J
GJ
Ransohoff
Richard M
RM
Chensue
Stephen W
SW
Raine
Cedric S
CS
Lira
Sergio A
SA
D000208:Acute Disease; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D004318:Doxycycline / Q000633:toxicity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D007958:Leukocyte Count; D008024:Ligands; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008590:Meningoencephalitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D008024:Ligands; D008565:Membrane Proteins; D004676:Myelin Basic Protein; C084881:flt3 ligand protein; D004318:Doxycycline