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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

Perturbation of iNKT differentiation and lipid antigen presentation in clonal hematopoiesis implies novel therapeutic targets.

Key Points

  • This study investigates the impact of TET2 loss on iNKT cell function in the context of clonal hematopoiesis.
  • Evaluated iNKT cells in Tet2-deficient murine chimeras.
  • Utilized single-cell RNA sequencing to analyze iNKT cell transcriptomes.
  • Performed lipidomic profiling to assess changes in lipid antigen presentation on CD1d.
  • Assessed cytokine profiles in plasma of Tet2KO mice.
  • Tet2KO chimeras showed significant loss of peripheral iNKT cells correlated with TET2-deficient hematopoiesis.
  • Increased IL-6 levels in Tet2KO plasma linked to iNKT17 differentiation.
  • Significant alterations in lipid composition affecting CD1d presentation were identified.

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. 1Metabolic control of innate immune activation in TET2-mutant clonal hematopoiesis2026 · 2 citations
  2. 2Compartmentalized inflammatory landscape and macrophage plasticity regulate Tet2+/- mediated clonal hematopoiesis2026 · 2 citations
  3. 3TET2 mutations drive cell-autonomous type I interferon production and selective advantage through TRIM4 silencing2025
  4. 4Accelerated adverse cardiac remodeling in a model of TET2 mutation-driven clonal hematopoiesis is ameliorated by IFNa treatment by modulating the monocyte response2025
  5. 5Human TET2-mutant clonal hematopoiesis expansion is driven by distinct inflammatory signaling responses in stem cells versus myeloid progeny.2025 · 8 citations