The Role of IFN‐γ‐Mediated Immune Cell Crosstalk in the Pathogenesis of Aplastic Anemia

Interferon-gamma (IFN-γ) is a central mediator of immune-driven bone marrow failure (BMF) in acquired aplastic anemia (AA). Persistent IFN-γ signaling alters the bone marrow microenvironment by activating the JAK-STAT1 pathway, which results in immunological imbalance, inflammatory amplification, and depletion of hematopoietic stem and progenitor cells (HSPCs). IFN-γ disturbs HSPC quiescence and self-renewal, interferes with thrombopoietin (TPO)-c-Mpl communication, and stimulates cytotoxic T-cell-dominant immunological responses. Simultaneously, IFN-γ destabilizes local immunological homeostasis by disrupting immune crosstalk through the IDO1 axis and regulatory T-cell (Treg) malfunction. In addition to discussing new therapeutic methods, such as Treg-based therapies and JAK inhibition, as prospective precision approaches for AA, this review incorporates current mechanistic insights into IFN-γ-driven cellular interactions inside the bone marrow niche.