An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism

Zhang, Zengdi; Salgado, Oscar Camilo; Liu, Bing; Moazzami, Zahra; Hogquist, Kristin A.; Farrar, Michael A.; Ruan, Hai‐Bin

doi:10.3389/fimmu.2022.874863

Cited by 5 publications

(6 citation statements)

References 60 publications

(79 reference statements)

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“…6i) 63,64 . Other transcription factors, including STAT5A, and cAMPinducible factors, such as CREB1 and CEBPB, which were related to metabolic fitness of Tregs 65,66 , might ensure functional specialization of Tregs in the NPC microenvironment (Fig. 6i).…”

Section: Mitochondrial Integrity Cholesterol Homeostasis and Fatty Ac...mentioning

confidence: 99%

Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction

et al. 2023

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Despite the intense CD8+ T-cell infiltration in the tumor microenvironment of nasopharyngeal carcinoma, anti-PD-1 immunotherapy shows an unsatisfactory response rate in clinical trials, hindered by immunosuppressive signals. To understand how microenvironmental characteristics alter immune homeostasis and limit immunotherapy efficacy in nasopharyngeal carcinoma, here we establish a multi-center single-cell cohort based on public data, containing 357,206 cells from 50 patient samples. We reveal that nasopharyngeal carcinoma cells enhance development and suppressive activity of regulatory T cells via CD70-CD27 interaction. CD70 blocking reverts Treg-mediated suppression and thus reinvigorate CD8+ T-cell immunity. Anti-CD70+ anti-PD-1 therapy is evaluated in xenograft-derived organoids and humanized mice, exhibiting an improved tumor-killing efficacy. Mechanistically, CD70 knockout inhibits a collective lipid signaling network in CD4+ naïve and regulatory T cells involving mitochondrial integrity, cholesterol homeostasis, and fatty acid metabolism. Furthermore, ATAC-Seq delineates that CD70 is transcriptionally upregulated by NFKB2 via an Epstein-Barr virus-dependent epigenetic modification. Our findings identify CD70+ nasopharyngeal carcinoma cells as a metabolic switch that enforces the lipid-driven development, functional specialization and homeostasis of Tregs, leading to immune evasion. This study also demonstrates that CD70 blockade can act synergistically with anti-PD-1 treatment to reinvigorate T-cell immunity against nasopharyngeal carcinoma.

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Section: Mitochondrial Integrity Cholesterol Homeostasis and Fatty Ac...mentioning

confidence: 99%

Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction

et al. 2023

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“…Regulatory T cells (Treg) are immunosuppressive lymphocytes that control self-tolerance, in ammatory response, and tissue homeostasis. Study has indicated that Treg cell activation can inhibit fatty acid uptake in adipose tissue and reshape systemic iron metabolism [45]. Monocytes are a crucial component of innate immune response.…”

Section: Discussionmentioning

confidence: 99%

Causal relationships between immune cells and iron deficiency anemia: a bidirectional Mendelian randomization study

xu,

li,

Liu

et al. 2024

Preprint

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Background Observational studies have shown a potential link between immune factors and the risk of iron deficiency anemia (IDA), yet the causal relationship between immune cells and IDA remains enigmatic. Herein, we used Mendelian randomization (MR) to assess whether this association is causal. Methods We selected IDA genetic variants, including 8376 samples and 9810691 single nucleotide polymorphisms, and immune cells from a large open genome-wide association study (GWAS) for a bidirectional MR study. The primary method was inverse variance weighting (IVW), and auxiliary analyses were MR-Egger, weighted median, simple mode and weighted mode. The reliability of the results was subsequently verified by heterogeneity and sensitivity analysis. Results IVW method showed that 19 types of immune cells may be the risk factors of IDA, whereas 15 types of immune cells are the protective factors of IDA. Reverse MR analysis suggested that immune cells from upstream etiology of IDA are not involved in follow-up immune activities. Next, we selected 731 immune cell types as the results. The research revealed that IDA may result in a rise in 23 kinds of immune cells and a reduction in 12 kinds of immune cells. In addition, sensitivity analysis demonstrated no evidence of heterogeneity or horizontal pleiotropy. Conclusions From a genetic standpoint, our study suggests that specific immune cells are involved in the occurrence of IDA. Inversely, IDA may also contribute to immune dysfunction, thus guiding future clinical investigations.

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“…O-GlcNAcylation was also shown to be essential for lineage stability and T cell suppressive function in Treg cells. TCR-induced O-GlcNAcylation was shown to stabilize FOXP3 and activate STAT5 ( 15 ), as well as regulate insulin sensitivity and iron metabolism in Treg cells in a STAT5-dependent manner ( 89 ). Like Treg cells, MSC are also involved in suppressing T cells to maintain homeostasis.…”

Section: O-glcnacylation and Immunometabolismmentioning

confidence: 99%

O-GlcNAcylation and immune cell signaling: A review of known and a preview of unknown

Ramakrishnan

2024

Journal of Biological Chemistry

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An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism

Cited by 5 publications

References 60 publications

Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction

Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction

Causal relationships between immune cells and iron deficiency anemia: a bidirectional Mendelian randomization study

O-GlcNAcylation and immune cell signaling: A review of known and a preview of unknown

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