Interferon tau

IFN-τ is constitutively secreted by trophoblast and endometrial cells during ovine pregnancy. Its secretion begins around tenth day and increases between days 13 and 16, when it reaches its peak, and then stopping after day 24 of pregnancy. IFN-τ is essential to maintain the levels of progesterone production by the corpus luteum for the maternal recognition of pregnancy, and together with progesterone increases expression of genes for transport of nutrients into the uterine lumen, growth factors for hematopoiesis and angiogenesis and other molecules that are crucial for implantation and placentation.^[1][10] It has both endocrine and paracrine effects, immunomodulatory influence on several types of cells including neutrophils, and antiproliferative, antiluteolytic and immunosuppressive effects on the endometrium.^[11][12]

IFN-τ binds to IFNAR cell membrane receptor and induces dimerization of its subunits, IFNAR1 and IFNAR2, which leads to activation of canonical and noncanonical signaling pathways. The canonical pathway involves Janus kinase-signal transducer and activator of transcription-interferon regulatory factor (JAK-STAT-IRF) signaling.^[13][14] This leads to induction of classical interferon stimulated genes (ISGs).^[15] The noncanonical signaling pathway includes mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase thymoma viral proto-onco- gene 1 (PI3K-AKT1) cascades.^[16]

IFN-τ can also stimulate expression of interleukins IL-6 and IL-8. However, the mechanism is not STAT1, but STAT3 dependent.^[17]

Synthetic gene for ovine IFN-τ was produced using Pichia pastoris yeast system. The recombinant IFN-τ had the same antiviral, antiluteolytic and immunosuppressive properties as native IFN-τ.^[2]

Understanding the role of IFN-τ in pregnancy recognition in ruminants and its mechanism of action led to its use in pregnancy diagnosis, as it can be measured directly from blood, and knowledge of its actions can be used to improve the reproductive efficiency in ruminants.^[18][19]

Since the effects of IFN-τ are not limited to ruminants and pregnancy, it has been studied for its anti-inflammatory properties as a treatment for diabetes.^[20][21] NOD mice that were treated with IFN-τ, which was administered either orally, intraperitoneally, or subcutaneously, have shown delayed or even inhibited development of diabetes.^[22]

IFN-τ is able to inhibit human immunodeficiency virus replication in vitro more effectively than human IFN-α. It was observed that IFN-τ decreased intracellular HIV RNA in human macrophages and inhibited reverse transcription of viral RNA into proviral DNA.^[23] Because of difference in both selectivity of individual N-termini towards receptors and different degree of receptor avidity, IFN-τ displays much less cytotoxicity than IFNT-α.^[7] This can be useful in treatment of viral diseases. IFN-τ has also demonstrated biological effects against influenza virus.^[24] However, IFN-τ has high species specificity which can cause a significant decrease in biological activity when administered to another species.^[25]