Potential role of iron in repair of inflammatory demyelinating lesions

Nathanael J. Lee, Seung Kwon Ha, Pascal Sati, Martina Absinta, Govind Nair, Nicholas J. Luciano, Emily C. Leibovitch, Cecil C. Yen, Tracey A. Rouault, Afonso C. Silva, Steven Jacobson, Daniel S. Reich

Research output: Contribution to journalArticle

Abstract

Inflammatory destruction of iron-rich myelin is characteristic of multiple sclerosis (MS). Although iron is needed for oligodendrocytes to produce myelin during development, its deposition has also been linked to neurodegeneration and inflammation, including in MS. We report perivascular iron deposition in multiple sclerosis lesions that was mirrored in 72 lesions from 13 marmosets with experimental autoimmune encephalomyelitis. Iron accumulated mainly inside microglia/ macrophages from 6 weeks after demyelination. Consistently, expression of transferrin receptor, the brain's main iron-influx protein, increased as lesions aged. Iron was uncorrelated with inflammation and postdated initial demyelination, suggesting that iron is not directly pathogenic. Iron homeostasis was at least partially restored in remyelinated, but not persistently demyelinated, lesions. Taken together, our results suggest that iron accumulation in the weeks after inflammatory demyelination may contribute to lesion repair rather than inflammatory demyelination per se.

Original languageEnglish (US)
Pages (from-to)4365-4376
Number of pages12
JournalJournal of Clinical Investigation
Volume129
Issue number10
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

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Iron
Demyelinating Diseases
Multiple Sclerosis
Myelin Sheath
Inflammation
Callithrix
Transferrin Receptors
Autoimmune Experimental Encephalomyelitis
Oligodendroglia
Microglia
Homeostasis
Macrophages
Brain
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lee, N. J., Ha, S. K., Sati, P., Absinta, M., Nair, G., Luciano, N. J., ... Reich, D. S. (2019). Potential role of iron in repair of inflammatory demyelinating lesions. Journal of Clinical Investigation, 129(10), 4365-4376. https://doi.org/10.1172/JCI126809

Potential role of iron in repair of inflammatory demyelinating lesions. / Lee, Nathanael J.; Ha, Seung Kwon; Sati, Pascal; Absinta, Martina; Nair, Govind; Luciano, Nicholas J.; Leibovitch, Emily C.; Yen, Cecil C.; Rouault, Tracey A.; Silva, Afonso C.; Jacobson, Steven; Reich, Daniel S.

In: Journal of Clinical Investigation, Vol. 129, No. 10, 01.10.2019, p. 4365-4376.

Research output: Contribution to journalArticle

Lee, NJ, Ha, SK, Sati, P, Absinta, M, Nair, G, Luciano, NJ, Leibovitch, EC, Yen, CC, Rouault, TA, Silva, AC, Jacobson, S & Reich, DS 2019, 'Potential role of iron in repair of inflammatory demyelinating lesions', Journal of Clinical Investigation, vol. 129, no. 10, pp. 4365-4376. https://doi.org/10.1172/JCI126809
Lee, Nathanael J. ; Ha, Seung Kwon ; Sati, Pascal ; Absinta, Martina ; Nair, Govind ; Luciano, Nicholas J. ; Leibovitch, Emily C. ; Yen, Cecil C. ; Rouault, Tracey A. ; Silva, Afonso C. ; Jacobson, Steven ; Reich, Daniel S. / Potential role of iron in repair of inflammatory demyelinating lesions. In: Journal of Clinical Investigation. 2019 ; Vol. 129, No. 10. pp. 4365-4376.
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AU - Leibovitch, Emily C.

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