Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival

Jenny S. Henkel, David R. Beers, Shixiang Wen, Andreana L. Rivera, Karen M. Toennis, Joan E. Appel, Weihua Zhao, Dan H. Moore, Suzanne Z. Powell, Stanley H. Appel

Research output: Contribution to journalArticlepeer-review

188 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)64-79
Number of pages16
JournalEMBO Molecular Medicine
Volume5
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • ALS
  • FoxP3
  • Gata3
  • Survival
  • Tregs

ASJC Scopus subject areas

  • Molecular Medicine

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