IFN-tau: a novel subtype I IFN1. Structural characteristics, non-ubiquitous expression, structure-function relationships, a pregnancy hormonal embryonic signal and cross-species therapeutic potentialities.
IFN-tau (IFN-tau) constitutes a new class of type I IFN which is not virus-inducible, unlike IFN-alpha and IFN-beta, but is constitutively produced by the trophectoderm of the ruminant conceptus during a very short period in early pregnancy. It plays a pivotal role in the mechanisms of maternal recognition of pregnancy in ruminants and it displays high antiviral and antiproliferative activities across species with a prominent lack of cytotoxicity at high concentrations in vitro in cell culture and possibly in vivo. It exhibits high antiretroviral activity against HIV and exhibits immunosuppressive activity in a multiple sclerosis model and reduces embryo and fetal mortality by stimulation of IL-10 production. In this review all the biochemical and para-hormonal properties of this novel IFN-tau are described in detail: structural characteristics of proteins and genes, trophoblast expression, regulation of its expression, structure of its gene promoter, its absence in human species and in non-ruminant animals, the evolution of the IFN-tau genes, its structure-function relationships with its three-dimensional structure, structural localization of biological activities, its lack of cytotoxicity and its receptor. Surprisingly, for an IFN, IFN-tau is also a pregnancy-embryonic signal with paracrine antiluteolytic activity. In order to maintain luteal progesterone secretion, IFN-tau inhibits PGF-2alpha pulsatile secretion and oxytocin uterine receptivity in early pregnancy. It is believed to suppress pulsatile release of endometrial PGF-2alpha by preventing oxytocin and estrogen receptor expression. Additionally, it directly regulates prostaglandin metabolism and possibly the PGE:PGF-2alpha ratio.
Martal
J L
JL
Inra, Station de Physiologie animale, Unité Endocrinologie de l'Embryon, Jouy-en-Josas, France.
Chêne
N M
NM
Huynh
L P
LP
L'Haridon
R M
RM
Reinaud
P B
PB
Guillomot
M W
MW
Charlier
M A
MA
Charpigny
S Y
SY
D000818:Animals; D005260:Female; D015870:Gene Expression; D006728:Hormones / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011270:Pregnancy, Animal / Q000502:physiology*; D017471:Receptors, Interferon / Q000502:physiology; D012418:Ruminants; D015398:Signal Transduction; D014452:Ubiquitins
D006728:Hormones; D007370:Interferon Type I; D011257:Pregnancy Proteins; D017471:Receptors, Interferon; D014452:Ubiquitins; C020947:interferon tau; C103636:interferon tau receptor