title: Developmental maturation of innate immune cell function correlates with susceptibility to central nervous system autoimmunity.
abstract: MS is an inflammatory CNS disorder, which typically occurs in early adulthood and rarely in children. Here we tested whether functional maturation of innate immune cells may determine susceptibility to CNS autoimmune disease in EAE. Two-week-old mice were resistant to active EAE, which causes fulminant paralysis in adult mice; this resistance was associated with an impaired development of Th1 and Th17 cells. Resistant, young mice had higher frequencies of myeloid-derived suppressor cells and plasma-cytoid DCs. Furthermore, myeloid APCs and B cells from young mice expressed lower levels of MHC class II and CD40, produced decreased amounts of proinflammatory cytokines, and released enhanced levels of anti-inflammatory IL-10. When used as APCs, splenocytes from 2-week-old mice failed to differentiate naive T cells into Th1 and Th17 cells irrespective of the T-cell donor's age, and promoted development of Treg cells and Th2 cells instead. Adoptive transfer of adult APCs restored the ability of 2-week-old mice to generate encephalitogenic T cells and develop EAE. Collectively, these findings indicate that the innate immune compartment functionally matures during development, which may be a prerequisite for development of T-cell-mediated CNS autoimmune disease.
authors: Department of Neurology, Technische Universität München, Munich, Germany.
authors: Deetje
authors: D
authors: Hertzenberg
authors: Klaus
authors: K
authors: Lehmann-Horn
authors: Silke
authors: S
authors: Kinzel
authors: Veronika
authors: V
authors: Husterer
authors: Petra D
authors: PD
authors: Cravens
authors: Bernd C
authors: BC
authors: Kieseier
authors: Bernhard
authors: B
authors: Hemmer
authors: Wolfgang
authors: W
authors: Brück
authors: Scott S
authors: SS
authors: Zamvil
authors: Olaf
authors: O
authors: Stüve
authors: Martin S
authors: MS
authors: Weber
mesh_terms: D019264:Adoptive Transfer; D000367:Age Factors; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000637:transplantation; D015551:Autoimmunity; D019013:CD40 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002490:Central Nervous System / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10
keywords: Age; Experimental autoimmune encephalomyelitis; Innate immunity; Multiple sclerosis; Susceptibility
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