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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 Gata3 mRNA expression levels are reduced in rapidly progressing ALS patientsqRT-PCR was utilized to evaluate expression levels of Gata3 mRNA isolated from leukocytes of ALS patients and control volunteers.A,B. Gata3 mRNA expression was decreased in rapidly progressing ALS patients (t-test) and inversely correlated with rate of disease progression (R = 0.405; linear regression).C. Gata3 and FoxP3 levels correlated (R = 0.737; linear regression).D. Gata3 and CD25 mRNA levels correlated (R = 0.810; linear regression). Note that slowly progressing patients early in their disease expressed the highest Gata3 mRNA levels, whereas rapidly progressing patients late in their course of disease expressed the lowest levels of Gata3 levels. ###p = 0.003 versus slowly progressing ALS patients; ***p = 0.00001 versus controls; &&&p ≤ 0.004.
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fig04: Leukocyte Gata3 mRNA expression levels are reduced in rapidly progressing ALS patientsqRT-PCR was utilized to evaluate expression levels of Gata3 mRNA isolated from leukocytes of ALS patients and control volunteers.A,B. Gata3 mRNA expression was decreased in rapidly progressing ALS patients (t-test) and inversely correlated with rate of disease progression (R = 0.405; linear regression).C. Gata3 and FoxP3 levels correlated (R = 0.737; linear regression).D. Gata3 and CD25 mRNA levels correlated (R = 0.810; linear regression). Note that slowly progressing patients early in their disease expressed the highest Gata3 mRNA levels, whereas rapidly progressing patients late in their course of disease expressed the lowest levels of Gata3 levels. ###p = 0.003 versus slowly progressing ALS patients; ***p = 0.00001 versus controls; &&&p ≤ 0.004.

Mentions: As Th2 lymphocytes are also neuroprotective in the ALS mouse (Beers et al, 2011b), we addressed whether Gata3, the master transcription factor for Th2 lymphocytes (Zhu & Paul, 2010) might also be affected. Gata3 levels in rapidly progressing patients were reduced 47% compared with slowly progressing patients (p = 0.003) and 57% compared with control volunteers (p = 0.00001; Fig 4A). Gata3 levels in ALS patients' leukocytes were inversely correlated with disease progression rates (p = 0.004; Fig 4B). Gata3 levels also directly correlated with FoxP3 and CD25 levels (both p < 0.001; Fig 4C and D).


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 Gata3 mRNA expression levels are reduced in rapidly progressing ALS patientsqRT-PCR was utilized to evaluate expression levels of Gata3 mRNA isolated from leukocytes of ALS patients and control volunteers.A,B. Gata3 mRNA expression was decreased in rapidly progressing ALS patients (t-test) and inversely correlated with rate of disease progression (R = 0.405; linear regression).C. Gata3 and FoxP3 levels correlated (R = 0.737; linear regression).D. Gata3 and CD25 mRNA levels correlated (R = 0.810; linear regression). Note that slowly progressing patients early in their disease expressed the highest Gata3 mRNA levels, whereas rapidly progressing patients late in their course of disease expressed the lowest levels of Gata3 levels. ###p = 0.003 versus slowly progressing ALS patients; ***p = 0.00001 versus controls; &&&p ≤ 0.004.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig04: Leukocyte Gata3 mRNA expression levels are reduced in rapidly progressing ALS patientsqRT-PCR was utilized to evaluate expression levels of Gata3 mRNA isolated from leukocytes of ALS patients and control volunteers.A,B. Gata3 mRNA expression was decreased in rapidly progressing ALS patients (t-test) and inversely correlated with rate of disease progression (R = 0.405; linear regression).C. Gata3 and FoxP3 levels correlated (R = 0.737; linear regression).D. Gata3 and CD25 mRNA levels correlated (R = 0.810; linear regression). Note that slowly progressing patients early in their disease expressed the highest Gata3 mRNA levels, whereas rapidly progressing patients late in their course of disease expressed the lowest levels of Gata3 levels. ###p = 0.003 versus slowly progressing ALS patients; ***p = 0.00001 versus controls; &&&p ≤ 0.004.
Mentions: As Th2 lymphocytes are also neuroprotective in the ALS mouse (Beers et al, 2011b), we addressed whether Gata3, the master transcription factor for Th2 lymphocytes (Zhu & Paul, 2010) might also be affected. Gata3 levels in rapidly progressing patients were reduced 47% compared with slowly progressing patients (p = 0.003) and 57% compared with control volunteers (p = 0.00001; Fig 4A). Gata3 levels in ALS patients' leukocytes were inversely correlated with disease progression rates (p = 0.004; Fig 4B). Gata3 levels also directly correlated with FoxP3 and CD25 levels (both p < 0.001; Fig 4C and D).

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