Paper Reading
01
A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8+ T cells
Ruihua Ma et al.
Nature cell biology. 2018
There is an important correlation between metabolic environment and long-term T cell memory.Previous studies showed that effector T cells use glycolysis for their growth and proliferation while memory T cells switch the metabolic pattern to oxidative phosphorylation via fatty acid oxidation. Although the important role of fatty acid oxidation in T-cell memory has been revealed, other intrinsic metabolic alterations and molecular pathways that mediate T cell memory formation and maintenance remain largely unknown. This article aimed to found out whether gluconeogenesis is involved in T cell memory homeostasis. They first found markedly upregulated Pck1(the enzyme converting OAA to PEP) and fructose-1,6-bisphosphatase (Fbp1, the enzyme converting fructose 1,6-bisphosphate to fructose 6-phosphate) protein level but not glucose-6-phosphatase level in CD8+ Tm cells, but not in naive (Tn) or Teff cells after infected the mice with Listeria monocytogenes expressing ovalbumin. And this phenomenon appears to be associated with the formation pf central memory T cells. Consequently, they observed much higher glycogen level in CD8+ Tm cells compared with CD8+ Tn or CD8+ Teff cells. But glycogecatalysing enzymes such as Pygl and Pygm were also upregulated in CD8+ Tm cells, suggesting that glycogen biosynthesis and degradation is an active process in CD8+ Tm cells. In addition, the memory-related transcription factors Tcf7, Lef1 and Bcl6 were downregulated after Pck1 inhibitor 3-MPA or glycogen phosphorylase inhibitor GPI treatment, indicated that Pck1 may influence Tm cell formation through enhancing the synthesis or accumulation of glycogen. 13C carbon tracing mass spectrometry showed Pck1-generated PEP flows to glycogen and PPP. Then they changed their focus to the events following glycogenolysis that impact on Tm formation to seek the mechanism. Data showed glycogen-derived G6P mediates the carbon flow toward PPP which resulted in increased NADPH，and this ensures high levels of reduced GSH which is essential for quenching ROS to facilitate the survival and fate maintenance of CD8+ Tm cells.
https://www.nature.com/articles/s41556-017-0002-2
02
Dendritic Cells Coordinate the Development and Homeostasis of Organ-Specific Regulatory T Cells
Daniel S. Leventhal, Dana C. Gilmore, Julian M. Berger et. al.
Immunity
Organ specific Treg cells have been suggested to be reactive to tissue restricted self-antigens, but the influences of TCR recognition by Treg cells like development and function, the cell types that present antigen to Treg cells in vivo remain largely undefined. In this article, authors first identified a clonal population of prostate-specific Treg cells, named “MJ23” Treg cells, that are enriched in the prostate-draining lymph nodes and prostate tumor lesions of male mice. Then, they found deficiency of CD80 and CD86 on radio resistant TECs led to a marked increase in the total number of polyclonal Treg cells in the thymus, which indicates CD80 and/or CD86 expression by TECs plays an important role in the negative selection of some specificities. They next assessed the requirement for antigen presentation by CD11c-expressing DCs, and found that antigen presentation by CD11c+ DCs is required to support MJ23 Treg cell development in the thymus. What is more, among all the three classes of DCs, they found that Plasmacytoid DCs and CD8α+ cDCs are dispensable for the thymic development of MJ23 Treg cells. Apart from DCs, they also elucidated the role of antigen recognition in dictating the peripheral homeostasis and anatomical distribution of MJ23 Treg cells and found that the enrichment of prostate-specific MJ23 Treg cells in the pLNs requires the continued presence of antigen. Because DCs are functionally different from each other, they also set to determine the subset of DCs involved in the antigen presentation to MJ23 Treg cells, and found that CCR7-dependent mDCs are required for the enrichment of MJ23 Treg cells in the pLNs of male mice.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842258/pdf/nihms-774119.pdf
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