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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.4
- 수록면
- 32 - 42 (11page)
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초록· 키워드
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During virus infection, T cells must be adapted to activation and lineage differentiation states via metabolic reprogramming. Whereas effector CD8+ T cells preferentially use glycolysis for their rapid proliferation, memory CD8+ T cells utilize oxidative phosphorylation for their homeostatic maintenance. Particularly, enhanced AMP-activated protein kinase (AMPK) activity promotes the memory T cell response through different pathways. However, the level of AMPK activation required for optimal memory T cell differentiation remains unclear. A new metformin derivative, IM156, formerly known as HL156A, has been reported to ameliorate various types of fibrosis and inhibit in vitro and in vivo tumors by inducing AMPK activation more potently than metformin. Here, we evaluated the in vivo effects of IM156 on antigen-specific CD8+ T cells during their effector and memory differentiation after acute lymphocytic choriomeningitis virus infection. Unexpectedly, our results showed that in vivo treatment of IM156 exacerbated the memory differentiation of virus-specific CD8+ T cells, resulting in an increase in short-lived effector cells but decrease in memory precursor effector cells. Thus, IM156 treatment impaired the function of virus-specific memory CD8+ T cells, indicating that excessive AMPK activation weakens memory T cell differentiation, thereby suppressing recall immune responses. This study suggests that metabolic reprogramming of antigen-specific CD8+ T cells by regulating the AMPK pathway should be carefully performed and managed to improve the efficacy of T cell vaccine.
목차
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
참고문헌 (22)
참고문헌 신청
O'Neill LA / 2016 / A guide to immunometabolism for immunologists / Nat Rev Immunol 16:553~565
Pearce EL / 2013 / Fueling immunity: insights into metabolism and lymphocyte function / Science 342:1242454
O'Sullivan D / 2015 / Targeting T cell metabolism for therapy / Trends Immunol 36:71~80
Buck MD / 2015 / T cell metabolism drives immunity / J Exp Med 212:1345~1360
Sukumar M / 2013 / Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function / J Clin Invest 123:4479~4488
Pearce EL / 2013 / Fueling immunity: insights into metabolism and lymphocyte function / Science 342:1242454
O'Sullivan D / 2015 / Targeting T cell metabolism for therapy / Trends Immunol 36:71~80
Buck MD / 2015 / T cell metabolism drives immunity / J Exp Med 212:1345~1360
Sukumar M / 2013 / Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function / J Clin Invest 123:4479~4488
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UCI(KEPA) : I410-ECN-0101-2019-517-000786735