Interferongammadriven

Interferon-gamma-driven refers to cellular responses, gene expression programs, and physiological outcomes that are largely regulated by the cytokine interferon-gamma (IFN-γ). It describes biological processes in which IFN-γ is the primary driver, produced by immune cells such as natural killer cells and T lymphocytes and acting to shape both innate and adaptive immunity.

Mechanism: IFN-γ signals through the IFN-γ receptor (IFNGR1/IFNGR2), activating the JAK1/JAK2-STAT1 pathway. Phosphorylated STAT1 dimerizes, translocates to the nucleus, and promotes transcription of gamma-activated genes. This program upregulates MHC class I and II expression, components of antigen processing such as TAP and immunoproteasome subunits LMP2, LMP7, and MECL-1, and the master regulator CIITA for MHC II. It enhances phagocyte antimicrobial activity via inducible nitric oxide synthase (iNOS) and reactive oxygen species, supports Th1 differentiation, and boosts cytotoxic T cell responses. IFN-γ also modulates chemokine expression and antigen presentation to strengthen adaptive immunity.

Physiological and clinical relevance: IFN-γ–driven responses are central to defense against intracellular pathogens (e.g., mycobacteria) and play a role in tumor immunosurveillance. Dysregulation can contribute to immunopathology and autoimmune conditions with Th1 features. IFN-γ–based diagnostics include assays measuring IFN-γ release by T cells in response to specific antigens. Therapeutically, IFN-γ is used in select immunodeficiencies and is an area of ongoing research in cancer immunotherapy.