Interferon tau and the immune blueprint of early ruminant pregnancy

Early embryonic loss remains a major constraint to reproductive efficiency in cattle, with a large proportion of failures occurring during early gestation, particularly across the peri-implantation period encompassing maternal recognition of pregnancy (MRP). During this critical window, conceptus-derived interferon tau (IFNT) acts as a key spatiotemporal regulator of immune and endocrine adaptation required for pregnancy establishment. Beyond its classical luteotropic role in preventing prostaglandin F₂α-mediated luteolysis, IFNT exerts cell- and compartment-specific immunomodulatory actions across the endometrium, corpus luteum (CL), and peripheral immune system. Within the uterus, IFNT induces tightly regulated interferon-stimulated gene (ISG) programs, restricts epithelial antigen presentation, modulates chemokine networks, and promote locally tolerogenic yet immunocompetent immune environment supportive of implantation. Systemically, circulating IFNT reaches maternal immune and endocrine compartments, inducing ISGs in peripheral blood mononuclear cells and neutrophils, biasing cytokine profiles toward immune regulation rather than overt inflammatory activation. Innate immune cells, particularly neutrophils and monocyte-derived macrophages, emerge as early IFNT-responsive populations, exhibiting restrained effector activity while contributing to immune-vascular remodeling and progesterone-supportive pathways within the CL. IFNT-responsive signaling is also evident within the CL itself, where immune-steroidogenic crosstalk and cell-survival pathways are associated with luteal maintenance during the maternal recognition period. Despite growing evidence, most current knowledge derives from correlative transcriptomic and in vitro studies, and the causal, cell-specific mechanisms linking IFNT-driven immune modulation to pregnancy establishment remain incompletely defined. This review integrates uterine, luteal, and systemic perspectives to position IFNT as a unifying immunoregulatory signal coordinating local and systemic immune adaptation during early ruminant pregnancy.