2022
DOI: 10.1126/sciimmunol.abl9467
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A central role for STAT5 in the transcriptional programing of T helper cell metabolism

Abstract: Activated lymphocytes adapt their metabolism to meet the energetic and biosynthetic demands imposed by rapid growth and proliferation. Common gamma chain (cγ) family cytokines are central to these processes, but the role of downstream signal transducer and activator of transcription 5 (STAT5) signaling, which is engaged by all cγ members, is poorly understood. Using genome-, transcriptome-, and metabolome-wide analyses, we demonstrate that STAT5 is a master regulator of energy and amino acid metabolism in CD4 … Show more

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Cited by 14 publications
(17 citation statements)
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“…6A ). While PIM1 and BCL2 are STAT5 target genes, BCL-2 is also independently regulated by the PI3K/AKT/mTOR pathway, which is in turn interwoven with STAT5 signaling in T-cell metabolism (45,56). T-ALL cells with high STAT5 activation were sensitive to JPX-0750 compared to control lung adenocarcinoma A549 cells ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…6A ). While PIM1 and BCL2 are STAT5 target genes, BCL-2 is also independently regulated by the PI3K/AKT/mTOR pathway, which is in turn interwoven with STAT5 signaling in T-cell metabolism (45,56). T-ALL cells with high STAT5 activation were sensitive to JPX-0750 compared to control lung adenocarcinoma A549 cells ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Its role in T cell metabolism has been studied for over 30 years but, as noted, that research has traditionally focused on downstream PI3-AKT and mTOR signaling. However, it is now apparent that STAT5 is also critical and, in fact, required for parallel mTOR activity [30]. For details on how PI3-AKT and mTOR influence cellular metabolism, we refer to comprehensive reviews [31,46].…”
Section: The Il-2-stat5 Axismentioning
confidence: 99%
“…In almost all cases, there is evidence that downstream STAT5 signaling instructs expression of relevant transporters, such as GLUT1, SLC1A5, the principal transporter for glutamine, and SLC7A5, the principal transporter for essential amino acids (Fig. 1) [30,45,48,49]. Second, IL-2 rapidly and potently induces glycolysis, glutaminolysis, and OxPhos, enabling cells to burn their newly obtained fuels [47,50,51].…”
Section: The Il-2-stat5 Axismentioning
confidence: 99%
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