RISS 검색 - 국내학술지논문

무료
기관 내 무료
유료

내보내기
내책장담기
한글로보기

정확도순

내림차순

내림차순

10개씩 출력

1
Regulator of Fatty Acid Metabolism, Acetyl Coenzyme A Carboxylase 1, Controls T Cell Immunity

Lee, JangEun,Walsh, Matthew C.,Hoehn, Kyle L.,James, David E.,Wherry, E. John,Choi, Yongwon American Association of Immunologists 2014 Journal of Immunology Vol. No.
- 원문보기
Fatty acids (FAs) are essential constituents of cell membranes, signaling molecules, and bioenergetic substrates. Because CD8+ T cells undergo both functional and metabolic changes during activation and differentiation, dynamic changes in FA metabolism also occur. However, the contributions of de novo lipogenesis to acquisition and maintenance of CD8+ T cell function are unclear. In this article, we demonstrate the role of FA synthesis in CD8+ T cell immunity. T cell–specific deletion of acetyl coenzyme A carboxylase 1 (ACC1), an enzyme that catalyzes conversion of acetyl coenzyme A to malonyl coenzyme A, a carbon donor for long-chain FA synthesis, resulted in impaired peripheral persistence and homeostatic proliferation of CD8+ T cells in naive mice. Loss of ACC1 did not compromise effector CD8+ T cell differentiation upon listeria infection but did result in a severe defect in Ag-specific CD8+ T cell accumulation because of increased death of proliferating cells. Furthermore, in vitro mitogenic stimulation demonstrated that defective blasting and survival of ACC1-deficient CD8+ T cells could be rescued by provision of exogenous FA. These results suggest an essential role for ACC1-mediated de novo lipogenesis as a regulator of CD8+ T cell expansion, and may provide insights for therapeutic targets for interventions in autoimmune diseases, cancer, and chronic infections.
2
Transient expression of ZBTB32 in anti-viral CD8 + T cells limits the magnitude of the effector response and the generation of memory

Shin, Hyun Mu,Kapoor, Varun N.,Kim, Gwanghun,Li, Peng,Kim, Hang-Rae,Suresh, M.,Kaech, Susan M.,Wherry, E. John,Selin, Liisa K.,Leonard, Warren J.,Welsh, Raymond M.,Berg, Leslie J. Public Library of Science 2017 PLoS pathogens Vol.13 No.8
- 원문보기
<▼1>Virus infections induce CD8+ T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8+ T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8+ T cells. After acute virus infection, CD8+ T cells deficient in ZBTB32 showed enhanced virus-specific CD8+ T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation. The dysregulation of CD8+ T cell responses in the absence of ZBTB32 was catastrophic, as Zbtb32-/- mice succumbed to a systemic viral infection and showed evidence of severe lung pathology. We found that ZBTB32 and Blimp-1 were co-expressed following CD8+ T cell activation, bound to each other, and cooperatively regulated Blimp-1 target genes Eomes and Cd27. These findings demonstrate that ZBTB32 is a key transcription factor in CD8+ effector T cells that is required for the balanced regulation of effector versus memory responses to infection.</▼1><▼2>Author summaryCD8+ T lymphocytes are essential for immune protection against viruses. In response to an infection, these cells are activated, proliferate, and generate antiviral effector cells that eradicate the infection. Following this, the majority of these effector cells die, leaving a small subset of long-lived virus-specific memory T cells. Our study identifies a transcription factor, ZBTB32, that is required for the regulation of CD8+ T cell responses. In its absence, antiviral CD8+ T cell numbers increase to abnormally high levels, and generate an overabundance of memory T cells. When this dysregulated response occurs following infection with a virus that cannot be rapidly eliminated by the immune system, the infected animals die from immune-mediated tissue damage, indicating the importance of this pathway.</▼2>

내보내기
내책장담기
한글로보기

정확도순

내림차순

내림차순

10개씩 출력

맨처음 페이지로 1 맨끝 페이지로

상세검색

RISS 보유자료

상세검색

해외전자자료

연관 검색어 추천