2. Academic Validation
  3. Ammonia detoxification promotes CD8+ T cell memory development by urea and citrulline cycles

Ammonia detoxification promotes CD8+ T cell memory development by urea and citrulline cycles

  • Nat Immunol. 2023 Jan;24(1):162-173. doi: 10.1038/s41590-022-01365-1.
Ke Tang # 1 2,  Huafeng Zhang # 3,  Jinghui Deng # 1,  Dianheng Wang 4,  Shichuan Liu 1,  Shuya Lu 1,  Qingfa Cui 1,  Chen Chen 1,  Jincheng Liu 1,  Zhuoshun Yang 1,  Yonggang Li 5,  Jie Chen 4,  Jiadi Lv 4,  Jingwei Ma 6,  Bo Huang 7 8
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Cell Architecture Research Center, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
  • 5 Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.
  • 6 Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 7 Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. tjhuangbo@hotmail.com.
  • 8 Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China. tjhuangbo@hotmail.com.
  • # Contributed equally.
PMID: 36471170 DOI: 10.1038/s41590-022-01365-1
Abstract

Amino acid metabolism is essential for cell survival, while the byproduct ammonia is toxic and can injure cellular longevity. Here we show that CD8+ memory T (TM) cells mobilize the carbamoyl phosphate (CP) metabolic pathway to clear ammonia, thus promoting memory development. CD8+ TM cells use β-hydroxybutyrylation to upregulate CP synthetase 1 and trigger the CP metabolic cascade to form arginine in the cytosol. This cytosolic arginine is then translocated into the mitochondria where it is split by Arginase 2 to urea and ornithine. Cytosolic arginine is also converted to nitric oxide and citrulline by nitric oxide synthases. Thus, both the urea and citrulline cycles are employed by CD8+ T cells to clear ammonia and enable memory development. This ammonia clearance machinery might be targeted to improve T cell-based Cancer immunotherapies.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z