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.
Tan et al. (Thu,) studied this question.