Autonomic denervation of lymphoid organs leads to epigenetic immune atrophy in a mouse model of Krabbe disease

Francesca Galbiati, Veronica Basso, Ludovico Cantuti, Maria Irene Givogri, Aurora Lopez-Rosas, Nicolas Perez, Chenthamarakshan Vasu, Hongmei Cao, Richard Van Breemen, Anna Mondino, Ernesto R. Bongarzone

Research output: Contribution to journalArticle

Abstract

Lysosomal β-galactosylceramidase deficiency results in demyelination and inflammation in the nervous system causing the neurological Krabbe disease. In the Twitcher mouse model of this disease, we found that neurological symptoms parallel progressive and severe lymphopenia. Although lymphopoiesis is normal before disease onset, primary and secondary lymphoid organs progressively degenerate afterward. This occurs despite preserved erythropoiesis and leads to severe peripheral lymphopenia caused by reduced numbers of T cell precursors and mature lymphocytes. Hematopoietic cell replacement experiments support the existence of an epigenetic factor in mutant mice reconcilable with a progressive loss of autonomic axons that hampers thymic functionality. We propose that degeneration of autonomic nerves leads to the irreversible thymic atrophy and loss of immune-competence. Our study describes a new aspect of Krabbe disease, placing patients at risk of immune-related pathologies, and identifies a novel target for therapeutic interventions.

Original languageEnglish
Pages (from-to)13730-13738
Number of pages9
JournalJournal of Neuroscience
Volume27
Issue number50
DOIs
Publication statusPublished - Dec 12 2007

Keywords

  • Autonomic system
  • Axonal degeneration
  • Hematopoietic stem cells
  • Inflammation
  • Krabbe disease
  • Psychosine
  • T cells
  • Thymus

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Galbiati, F., Basso, V., Cantuti, L., Givogri, M. I., Lopez-Rosas, A., Perez, N., Vasu, C., Cao, H., Van Breemen, R., Mondino, A., & Bongarzone, E. R. (2007). Autonomic denervation of lymphoid organs leads to epigenetic immune atrophy in a mouse model of Krabbe disease. Journal of Neuroscience, 27(50), 13730-13738. https://doi.org/10.1523/JNEUROSCI.3379-07.2007