Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival
Article first published online: 9 NOV 2012
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 1, pages 64–79, January 2013
How to Cite
Henkel, J. S., Beers, D. R., Wen, S., Rivera, A. L., Toennis, K. M., Appel, J. E., Zhao, W., Moore, D. H., Powell, S. Z. and Appel, S. H. (2013), Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. EMBO Mol Med, 5: 64–79. doi: 10.1002/emmm.201201544
- Issue published online: 3 JAN 2013
- Article first published online: 9 NOV 2012
- Manuscript Accepted: 27 SEP 2012
- Manuscript Revised: 22 AUG 2012
- Manuscript Received: 5 MAY 2012
- Funded Access
In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are neuroprotective, slowing disease progression. To address whether Tregs and FoxP3, a transcription factor required for Treg function, similarly influence progression rates of ALS patients, T-lymphocytes from patients were assessed by flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were reduced in rapidly progressing ALS patients and inversely correlated with progression rates. The mRNA levels of FoxP3, TGF-β, IL4 and Gata3, a Th2 transcription factor, were reduced in rapidly progressing patients and inversely correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients. A 3.5-year prospective study with a second larger cohort revealed that early reduced FoxP3 levels were indicative of progression rates at collection and predictive of future rapid progression and attenuated survival. Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients.