T2D PBMC TNF/NF-kB and IFN-Gamma Signaling
Zhao and Fang 2025 add a small-cohort PBMC scRNA-seq signal in which T2D T cells and monocytes show inflammatory pathway associations centered on TNF/NF-kB, interferon-gamma response, T-cell receptor signaling, and chemokine signaling.
Key Ideas
- Zhao and Fang 2025 report 3188 PBMC marker genes across 13,591 retained cells, with marker-gene pathway findings involving NF-kB, HIF-1, and TNF signaling. 1
- In T cells, Zhao and Fang 2025 report 119 DEGs in T2DM versus healthy controls, with GO terms including leukocyte chemotaxis, T-cell receptor signaling, and immune response-regulating signaling. 1
- Zhao and Fang 2025 report that T-cell GSEA highlighted HALLMARK_TNFA_SIGNALING_VIA_NFKB and that WGCNA connected T-cell modules with fasting glucose, fasting insulin, and HOMA-IR. 1
- Zhao and Fang 2025 identify TNFRSF1A as the core interaction gene in a T-cell WGCNA module associated with clinical indicators. 1
- In monocytes, Zhao and Fang 2025 report 175 DEGs and GSEA enrichment for HALLMARK_INTERFERON_GAMMA_RESPONSE. 1
- Zhao and Fang 2025 report that a monocyte module associated with fasting glucose was enriched for chemokine signaling. 1
Project Interpretation
- The Zhao signal reinforces the broader PBMC immune changes in T2D theme that inflammatory signaling is visible in blood immune-cell compartments, but it should be weighted cautiously because the cohort has only 3 T2DM and 3 control participants.
- TNF/NF-kB and interferon-gamma pathway findings overlap conceptually with T2D monocyte inflammatory signatures and T-cell immune activation described in other PBMC studies.
- The source does not determine whether these pathway changes are driven by T2D status, BMI, glycemia, medications, center-specific effects, or ancestry-associated biology.
Use In Manuscript
- Use as small-cohort external support for the premise that T2D PBMC scRNA-seq can recover inflammatory T-cell and monocyte pathway signatures.
- Do not cite as direct evidence for ancestry-associated PBMC differences.
- Use the authors’ own limitation statement to justify careful wording around single-cell PBMC replication and external validation.
Links
- Zhao et al. 2025 Single-Cell PBMCs in T2D
- GSE255566
- PBMC Immune Changes in Type 2 Diabetes
- Single-Cell PBMC Profiling in Type 2 Diabetes
- T2D Monocyte Inflammatory Signature
- T2D Cytotoxic T-Cell Expansion
- Paper Evidence Map: T2D PBMC Ancestry
Related
- NF-kB Signaling — synthesis