Department of Animal Science, Texas A&M University, College Station, Texas, USA.
Department of Animal Science, University of Florida, Gainesville, Florida, USA.
Reproduction. 2017 Nov;154(5):F11-F20. doi: 10.1530/REP-17-0257. Epub 2017 Jul 26.
It has been 38 years since a protein, now known as interferon tau (IFNT), was discovered in ovine conceptus-conditioned culture medium. After 1979, purification and testing of native IFNT revealed its unique antiluteolyic activity to prevent the regression of corpora lutea on ovaries of nonpregnant ewes. Antiviral, antiproliferative and immunomodulatory properties of native and recombinant IFNT were demonstrated later. In addition, progesterone and IFNT were found to act cooperatively to silence expression of classical interferon stimulated genes in a cell-specific manner in ovine uterine luminal and superficial glandular epithelia. But, IFNT signaling through a STAT1/STAT2-independent pathway stimulates expression of genes, such as those for transport of glucose and amino acids, which are required for growth and development of the conceptus. Further, undefined mechanisms of action of IFNT are key to a servomechanism that allows ovine placental lactogen and placental growth hormone to affect the development of uterine glands and their expression of genes throughout gestation. IFNT also acts systemically to induce the expression of interferon stimulated genes that influence secretion of progesterone by the corpus luteum. Finally, IFNT has great potential as a therapeutic agent due to its low cytotoxicity, anti-inflammatory properties and effects to mitigate diabetes, obesity-associated syndromes and various autoimmune diseases.
自绵羊胚胎条件培养基中发现一种蛋白（现称为干扰素 tau，IFNT）以来，已经过去了 38 年。1979 年后，对天然 IFNT 的纯化和测试揭示了其独特的抗黄体溶解活性，可防止非妊娠母羊卵巢黄体的退化。随后还证明了天然和重组 IFNT 的抗病毒、抗增殖和免疫调节特性。此外，人们发现孕激素和 IFNT 以协同方式沉默经典干扰素刺激基因在绵羊子宫腔和表面腺上皮中的表达，具有细胞特异性。但是，IFNT 通过 STAT1/STAT2 非依赖性途径发出信号，刺激葡萄糖和氨基酸等运输基因的表达，这是胚胎生长和发育所必需的。此外，IFNT 的作用机制尚不清楚，这是一种伺服机制的关键，允许绵羊胎盘催乳素和胎盘生长激素影响整个妊娠期间子宫腺的发育及其基因表达。IFNT 还具有全身作用，可诱导干扰素刺激基因的表达，从而影响黄体分泌孕酮。最后，IFNT 具有作为治疗剂的巨大潜力，因为它具有低细胞毒性、抗炎特性以及减轻糖尿病、肥胖相关综合征和各种自身免疫性疾病的作用。
