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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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Leukocyte FoxP3 and CD25 mRNA expression levels are reduced in rapidly progressing ALS patientsqRT-PCR was utilized to evaluate mRNA expression levels of FoxP3 and CD25 in leukocytes obtained from 54 ALS patients through all stages of disease and 33 control volunteers.A,B. FoxP3 mRNA expression levels were down-regulated in rapidly progressing ALS patients (t-test) and negatively correlated with disease progression rates (R = 0.419; linear regression).C,D. CD25 mRNA expression levels were reduced in rapidly progressing ALS patients (t-test) and inversely correlated with rate of disease progression (R = 0.444; linear regression).E. FoxP3 and CD25 mRNA expression levels of ALS patients directly correlated with each other (R = 0.815; linear regression). Note that slowly progressing patients early in their disease expressed the highest FoxP3 and CD25 mRNA levels, whereas rapidly progressing patients late in their course of disease expressed the lowest levels of FoxP3 and CD25 mRNAs. ##p ≤ 0.005 versus slowly progressing ALS patients. ***p ≤ 0.001 versus controls. &&p ≤ 0.005, &&&p ≤ 0.001.
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fig03: Leukocyte FoxP3 and CD25 mRNA expression levels are reduced in rapidly progressing ALS patientsqRT-PCR was utilized to evaluate mRNA expression levels of FoxP3 and CD25 in leukocytes obtained from 54 ALS patients through all stages of disease and 33 control volunteers.A,B. FoxP3 mRNA expression levels were down-regulated in rapidly progressing ALS patients (t-test) and negatively correlated with disease progression rates (R = 0.419; linear regression).C,D. CD25 mRNA expression levels were reduced in rapidly progressing ALS patients (t-test) and inversely correlated with rate of disease progression (R = 0.444; linear regression).E. FoxP3 and CD25 mRNA expression levels of ALS patients directly correlated with each other (R = 0.815; linear regression). Note that slowly progressing patients early in their disease expressed the highest FoxP3 and CD25 mRNA levels, whereas rapidly progressing patients late in their course of disease expressed the lowest levels of FoxP3 and CD25 mRNAs. ##p ≤ 0.005 versus slowly progressing ALS patients. ***p ≤ 0.001 versus controls. &&p ≤ 0.005, &&&p ≤ 0.001.

Mentions: As an independent assessment, leukocyte FoxP3 and CD25 mRNA expression levels were also examined by quantitative (q)RT-PCR. FoxP3 mRNA levels from rapidly progressing patients were reduced 34% compared with slowly progressing patients (p = 0.001) and 44% compared with controls (p = 0.00002; Fig 3A). CD25 mRNA levels in leukocytes from rapidly progressing ALS patients were reduced 35% compared with slowly progressing patients (p = 0.006) and 45% compared with controls (p = 0.00003; Fig 3C). FoxP3 and CD25 mRNA levels in slowly progressing patients were not different than controls (p = 0.164, p = 0.211, respectively). Both the FoxP3 and CD25 expression levels in patients were inversely correlated with rates of progression (p = 0.003, p = 0.001, respectively; Fig 3B and D). CD25 mRNA expression levels directly correlated with FoxP3 mRNA levels (p < 0.001; Fig 3E); note that rapidly progressing patients late in their course of disease expressed the lowest levels of FoxP3 and CD25 mRNAs, whereas slowly progressing patients early in their disease expressed the highest FoxP3 and CD25 mRNA levels.


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)

Leukocyte FoxP3 and CD25 mRNA expression levels are reduced in rapidly progressing ALS patientsqRT-PCR was utilized to evaluate mRNA expression levels of FoxP3 and CD25 in leukocytes obtained from 54 ALS patients through all stages of disease and 33 control volunteers.A,B. FoxP3 mRNA expression levels were down-regulated in rapidly progressing ALS patients (t-test) and negatively correlated with disease progression rates (R = 0.419; linear regression).C,D. CD25 mRNA expression levels were reduced in rapidly progressing ALS patients (t-test) and inversely correlated with rate of disease progression (R = 0.444; linear regression).E. FoxP3 and CD25 mRNA expression levels of ALS patients directly correlated with each other (R = 0.815; linear regression). Note that slowly progressing patients early in their disease expressed the highest FoxP3 and CD25 mRNA levels, whereas rapidly progressing patients late in their course of disease expressed the lowest levels of FoxP3 and CD25 mRNAs. ##p ≤ 0.005 versus slowly progressing ALS patients. ***p ≤ 0.001 versus controls. &&p ≤ 0.005, &&&p ≤ 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig03: Leukocyte FoxP3 and CD25 mRNA expression levels are reduced in rapidly progressing ALS patientsqRT-PCR was utilized to evaluate mRNA expression levels of FoxP3 and CD25 in leukocytes obtained from 54 ALS patients through all stages of disease and 33 control volunteers.A,B. FoxP3 mRNA expression levels were down-regulated in rapidly progressing ALS patients (t-test) and negatively correlated with disease progression rates (R = 0.419; linear regression).C,D. CD25 mRNA expression levels were reduced in rapidly progressing ALS patients (t-test) and inversely correlated with rate of disease progression (R = 0.444; linear regression).E. FoxP3 and CD25 mRNA expression levels of ALS patients directly correlated with each other (R = 0.815; linear regression). Note that slowly progressing patients early in their disease expressed the highest FoxP3 and CD25 mRNA levels, whereas rapidly progressing patients late in their course of disease expressed the lowest levels of FoxP3 and CD25 mRNAs. ##p ≤ 0.005 versus slowly progressing ALS patients. ***p ≤ 0.001 versus controls. &&p ≤ 0.005, &&&p ≤ 0.001.
Mentions: As an independent assessment, leukocyte FoxP3 and CD25 mRNA expression levels were also examined by quantitative (q)RT-PCR. FoxP3 mRNA levels from rapidly progressing patients were reduced 34% compared with slowly progressing patients (p = 0.001) and 44% compared with controls (p = 0.00002; Fig 3A). CD25 mRNA levels in leukocytes from rapidly progressing ALS patients were reduced 35% compared with slowly progressing patients (p = 0.006) and 45% compared with controls (p = 0.00003; Fig 3C). FoxP3 and CD25 mRNA levels in slowly progressing patients were not different than controls (p = 0.164, p = 0.211, respectively). Both the FoxP3 and CD25 expression levels in patients were inversely correlated with rates of progression (p = 0.003, p = 0.001, respectively; Fig 3B and D). CD25 mRNA expression levels directly correlated with FoxP3 mRNA levels (p < 0.001; Fig 3E); note that rapidly progressing patients late in their course of disease expressed the lowest levels of FoxP3 and CD25 mRNAs, whereas slowly progressing patients early in their disease expressed the highest FoxP3 and CD25 mRNA levels.

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