GSDMD-dependent Stromal Pyroptosis Drives Maladaptive CD4⁺ T-cell Remodeling in Tet2-Deficient Hematopoiesis

Here, we show that stromal pyroptosis drives mutation-specific myeloid expansion by coordinating monocytic remodeling and CD4⁺ T-cell activation. Genetic ablation of gasdermin D in the bone marrow stroma suppressed stromal pyroptosis and attenuated Tet2-deficient myeloid expansion.

Tet2 deficiency skewed monocyte and macrophage differentiation toward an activated, antigen-presenting state that interacted with pyroptotic stromal cells to promote expansion of a distinct CD4⁺ T-cell population. These cells expressed canonical T follicular helper markers (Bcl6, Cxcr5, Il21, and Cd40l) together with interferon-responsive and tissue-interaction programs, consistent with an inflammation-adapted TFH-like (TFHL) state.