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Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival.

Henkel JS, Beers DR, Wen S, Rivera AL, Toennis KM, Appel JE, Zhao W, Moore DH, Powell SZ, Appel SH - EMBO Mol Med (2012)

Bottom Line: 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.No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients.Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Methodist Hospital Research Institute, Houston, TX, USA. jhenkel@tmhs.org

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FoxP3 intensity in CD4+FoxP3+ Tregs is reduced in rapidly progressing ALS patientsThere was a trend toward reduced numbers of CD4+FoxP3+ Tregs in the blood of rapidly progressing patients compared with both slowly progressing patients and control volunteers.FoxP3 intensity in CD4+FoxP3+ Tregs is reduced in rapidly progressing patients compared with slowly progressing patients and compared with control volunteers; slowly progressing patients were not different than controls. #p = 0.049 versus slowly progressing ALS patients; **p = 0.015 versus controls.
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fig02: FoxP3 intensity in CD4+FoxP3+ Tregs is reduced in rapidly progressing ALS patientsThere was a trend toward reduced numbers of CD4+FoxP3+ Tregs in the blood of rapidly progressing patients compared with both slowly progressing patients and control volunteers.FoxP3 intensity in CD4+FoxP3+ Tregs is reduced in rapidly progressing patients compared with slowly progressing patients and compared with control volunteers; slowly progressing patients were not different than controls. #p = 0.049 versus slowly progressing ALS patients; **p = 0.015 versus controls.

Mentions: The Treg transcription factor, FoxP3, is currently the most reliable marker for identifying Tregs. Therefore, CD4+FoxP3+ Tregs from the same 54 ALS patients were evaluated to determine whether CD4+FoxP3+ Tregs were also associated with disease progression. While not significant, there were trends toward reduced CD4+FoxP3+ Tregs in rapidly progressing patients compared with controls (p = 0.082) and slowly progressing patients (p = 0.196; Fig 2A). CD4+FoxP3+ Tregs from slowly progressing patients were not different than controls (p = 0.371). High FoxP3 expression is required for the suppressive function of Tregs (Sakaguchi et al, 2010); therefore, we also examined FoxP3 fluorescent intensity by flow cytometry, as an assessment of FoxP3 protein expression, in CD4+FoxP3+ Tregs. The FoxP3 fluorescent intensities in CD4+FoxP3+ Tregs were reduced in rapidly progressing patients compared with controls (p = 0.015; Fig 2B) and slowly progressing patients (p = 0.049) and inversely correlated with progression rates (p = 0.047). The FoxP3 fluorescent intensities in Tregs from slowly progressing patients were not different than controls (p = 0.296). Thus, as with CD4+CD25High Tregs numbers, there was a reduction in FoxP3 fluorescent intensity in CD4+FoxP3+ Tregs from rapidly progressing ALS patients.


Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival.

Henkel JS, Beers DR, Wen S, Rivera AL, Toennis KM, Appel JE, Zhao W, Moore DH, Powell SZ, Appel SH - EMBO Mol Med (2012)

FoxP3 intensity in CD4+FoxP3+ Tregs is reduced in rapidly progressing ALS patientsThere was a trend toward reduced numbers of CD4+FoxP3+ Tregs in the blood of rapidly progressing patients compared with both slowly progressing patients and control volunteers.FoxP3 intensity in CD4+FoxP3+ Tregs is reduced in rapidly progressing patients compared with slowly progressing patients and compared with control volunteers; slowly progressing patients were not different than controls. #p = 0.049 versus slowly progressing ALS patients; **p = 0.015 versus controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3569654&req=5

fig02: FoxP3 intensity in CD4+FoxP3+ Tregs is reduced in rapidly progressing ALS patientsThere was a trend toward reduced numbers of CD4+FoxP3+ Tregs in the blood of rapidly progressing patients compared with both slowly progressing patients and control volunteers.FoxP3 intensity in CD4+FoxP3+ Tregs is reduced in rapidly progressing patients compared with slowly progressing patients and compared with control volunteers; slowly progressing patients were not different than controls. #p = 0.049 versus slowly progressing ALS patients; **p = 0.015 versus controls.
Mentions: The Treg transcription factor, FoxP3, is currently the most reliable marker for identifying Tregs. Therefore, CD4+FoxP3+ Tregs from the same 54 ALS patients were evaluated to determine whether CD4+FoxP3+ Tregs were also associated with disease progression. While not significant, there were trends toward reduced CD4+FoxP3+ Tregs in rapidly progressing patients compared with controls (p = 0.082) and slowly progressing patients (p = 0.196; Fig 2A). CD4+FoxP3+ Tregs from slowly progressing patients were not different than controls (p = 0.371). High FoxP3 expression is required for the suppressive function of Tregs (Sakaguchi et al, 2010); therefore, we also examined FoxP3 fluorescent intensity by flow cytometry, as an assessment of FoxP3 protein expression, in CD4+FoxP3+ Tregs. The FoxP3 fluorescent intensities in CD4+FoxP3+ Tregs were reduced in rapidly progressing patients compared with controls (p = 0.015; Fig 2B) and slowly progressing patients (p = 0.049) and inversely correlated with progression rates (p = 0.047). The FoxP3 fluorescent intensities in Tregs from slowly progressing patients were not different than controls (p = 0.296). Thus, as with CD4+CD25High Tregs numbers, there was a reduction in FoxP3 fluorescent intensity in CD4+FoxP3+ Tregs from rapidly progressing ALS patients.

Bottom Line: 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.No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients.Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Methodist Hospital Research Institute, Houston, TX, USA. jhenkel@tmhs.org

Show MeSH
Related in: MedlinePlus