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December 8, 2025BloodOpen Access

Perturbation of iNKT differentiation during clonal hematopoiesis from rewiring of inflammation and lipid presentation

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Authors

PGParan GoelACAmanda CostaMBMolly Boettiger

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Overview

Observational analysis reveals TET2 mutations lead to skewed iNKT differentiation and inflammation in hematopoietic cells, indicating novel immunometabolic targets for therapy.

Key Points

  • TET2 loss skews iNKT cell differentiation toward an iNKT17 phenotype, compromising immune response.
  • Significant elevation of IL-6 was observed in Tet2-deficient mice, correlating with inflammatory activation.
  • Single-cell RNA sequencing and flow cytometry methods were employed to assess TET2's impact on iNKT cells.
  • Results highlight potential for targeting immune mechanisms in early clonal hematopoiesis and preleukemic conditions.

Cite This Study

Goel et al. (2025) studied this question.

synapsesocial.com/papers/69362f764fa91c937236e369https://doi.org/10.1182/blood-2025-978
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1TET2 mutations drive cell-autonomous type I interferon production and selective advantage through TRIM4 silencing2025
  2. 2Accelerated adverse cardiac remodeling in a model of TET2 mutation-driven clonal hematopoiesis is ameliorated by IFNa treatment by modulating the monocyte response2025
  3. 3Human TET2-mutant clonal hematopoiesis expansion is driven by distinct inflammatory signaling responses in stem cells versus myeloid progeny.2025 · 8 citations
  4. 4Single-cell multiomic profiling of gene mutation, chromatin accessibility, and gene expression in TET2-mutant clonal hematopoiesis2025
  5. 5Tet2 clonal hematopoiesis enhances thrombotic pathologies, increases platelet reactivity, and alters megakaryote function in the context of aging2025