Abstract
Interactions between immune effector cells of the central nervous system appear to directly or indirectly influence the progress/regression of multiple sclerosis (MS). Here, we report that glial STAT1 and a '3 are distinctively phosphorylated following the interaction of activated lymphocytes and glia, and this effect is significantly inhibited by glatiramer acetate (GA), a disease-modifying drug for MS. GA also reduces the activations of STAT1 and a '3 by MS-Associated stimuli such as IFNI 3 or LPS in primary glia, but not neurons. Experiments in IFNI 3-And IFNI 3 receptor-deficient mice revealed that GA-induced inhibitions of STAT signaling are independent of IFNI 3 and its receptor. Interestingly, GA induces the expression levels of suppressor of cytokine signaling-1 and a '3, representative negative regulators of STAT signaling in glia. We further found that GA attenuates the LPS-Triggered enhancement of IL-2, a highly produced cytokine in patients with active MS, in CD4 + T cells co-cultured with glia, but not in CD4 + T cells alone. Collectively, these results provide that activation of glial STATs is an essential event in the interaction between glia and T cells, which is a possible underlying mechanism of GA action in MS. These findings provide an insight for the development of targeted therapies against MS.
| Original language | English |
|---|---|
| Article number | 40484 |
| Journal | Scientific reports |
| Volume | 7 |
| DOIs | |
| Publication status | Published - 2017 Jan 17 |
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Glatiramer acetate attenuates the activation of CD4 + T cells by modulating STAT1 and â'3 signaling in glia. / Ahn, Ye Hyeon; Jeon, Sae Bom; Chang, Chi Young; Goh, Eun Ah; Kim, Sang Soo; Kim, Ho Jin; Song, Jaewhan; Park, Eun Jung.
In: Scientific reports, Vol. 7, 40484, 17.01.2017.Research output: Contribution to journal › Article
TY - JOUR
T1 - Glatiramer acetate attenuates the activation of CD4 + T cells by modulating STAT1 and â'3 signaling in glia
AU - Ahn, Ye Hyeon
AU - Jeon, Sae Bom
AU - Chang, Chi Young
AU - Goh, Eun Ah
AU - Kim, Sang Soo
AU - Kim, Ho Jin
AU - Song, Jaewhan
AU - Park, Eun Jung
PY - 2017/1/17
Y1 - 2017/1/17
N2 - Interactions between immune effector cells of the central nervous system appear to directly or indirectly influence the progress/regression of multiple sclerosis (MS). Here, we report that glial STAT1 and a '3 are distinctively phosphorylated following the interaction of activated lymphocytes and glia, and this effect is significantly inhibited by glatiramer acetate (GA), a disease-modifying drug for MS. GA also reduces the activations of STAT1 and a '3 by MS-Associated stimuli such as IFNI 3 or LPS in primary glia, but not neurons. Experiments in IFNI 3-And IFNI 3 receptor-deficient mice revealed that GA-induced inhibitions of STAT signaling are independent of IFNI 3 and its receptor. Interestingly, GA induces the expression levels of suppressor of cytokine signaling-1 and a '3, representative negative regulators of STAT signaling in glia. We further found that GA attenuates the LPS-Triggered enhancement of IL-2, a highly produced cytokine in patients with active MS, in CD4 + T cells co-cultured with glia, but not in CD4 + T cells alone. Collectively, these results provide that activation of glial STATs is an essential event in the interaction between glia and T cells, which is a possible underlying mechanism of GA action in MS. These findings provide an insight for the development of targeted therapies against MS.
AB - Interactions between immune effector cells of the central nervous system appear to directly or indirectly influence the progress/regression of multiple sclerosis (MS). Here, we report that glial STAT1 and a '3 are distinctively phosphorylated following the interaction of activated lymphocytes and glia, and this effect is significantly inhibited by glatiramer acetate (GA), a disease-modifying drug for MS. GA also reduces the activations of STAT1 and a '3 by MS-Associated stimuli such as IFNI 3 or LPS in primary glia, but not neurons. Experiments in IFNI 3-And IFNI 3 receptor-deficient mice revealed that GA-induced inhibitions of STAT signaling are independent of IFNI 3 and its receptor. Interestingly, GA induces the expression levels of suppressor of cytokine signaling-1 and a '3, representative negative regulators of STAT signaling in glia. We further found that GA attenuates the LPS-Triggered enhancement of IL-2, a highly produced cytokine in patients with active MS, in CD4 + T cells co-cultured with glia, but not in CD4 + T cells alone. Collectively, these results provide that activation of glial STATs is an essential event in the interaction between glia and T cells, which is a possible underlying mechanism of GA action in MS. These findings provide an insight for the development of targeted therapies against MS.
UR - http://www.scopus.com/inward/record.url?scp=85009936518&partnerID=8YFLogxK
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U2 - 10.1038/srep40484
DO - 10.1038/srep40484
M3 - Article
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 40484
ER -