Developmental maturation of innate immune cell function correlates with susceptibility to central nervous system autoimmunity

Deetje Hertzenberg, Klaus Lehmann-Horn, Silke Kinzel, Veronika Husterer, Petra D. Cravens, Bernd C. Kieseier, Bernhard Hemmer, Wolfgang Brück, Scott S. Zamvil, Olaf Stüve, Martin S. Weber

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2078-2088
Number of pages11
JournalEuropean Journal of Immunology
Volume43
Issue number8
DOIs
StatePublished - Aug 1 2013

Keywords

  • Age
  • Experimental autoimmune encephalomyelitis
  • Innate immunity
  • Multiple sclerosis
  • Susceptibility

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Hertzenberg, D., Lehmann-Horn, K., Kinzel, S., Husterer, V., Cravens, P. D., Kieseier, B. C., Hemmer, B., Brück, W., Zamvil, S. S., Stüve, O., & Weber, M. S. (2013). Developmental maturation of innate immune cell function correlates with susceptibility to central nervous system autoimmunity. European Journal of Immunology, 43(8), 2078-2088. https://doi.org/10.1002/eji.201343338