Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in mulitple sclerosis and autoimmune disorders

Khan, O.A.; Jiang, H.; Subramaniam, P.S.; Johnson, H.M.; Dhib-Jalbut, S.S.

doi:10.1191/135245898678919573

Cited by 8 publications

(4 citation statements)

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“…Ovine IFN'T possesses antiviral activity similar to IFNa across several species, inclUding humans (110). However, unlike IFNa and IFNI3, IFNT lacks toxicity for cells at high concentrations (110,112), and does not induce weight loss or bone marrow suppression in animal models (103,104,106). This is a very important observation for the use of type 1 IFNs as therapeutics, particularly for treatment of MS.…”

Section: Immune-based Therapies That Amelioratementioning

confidence: 99%

Superantigens: The Good, the Bad, and the Ugly

Torres

Kominsky

Perrin

et al. 2001

Exp Biol Med (Maywood)

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Increasing evidence suggests that superantlgens playa role In Immune-mediated diseases. Superantlgens are potent activators of CD4+T cells, causing rapid and massive proliferation of cells and cytoklne production. This characteristic of auperarmgens can be exploited In diseases where strong Immunologic responses are required, such as In the B16F10 animal model of melanoma. Superantlgen administration Is able to significantly enhance Ineffective anti-tumor Immune responses, resulting in potent and long-lived protective anti-tumor Immunity. However, superantlgens are more well-known for the role they play in diseases. Studies using an animal model for neurologic demyelinating diseases such as multiple sclerosis show that superantlgens can Induce severe relapses and activate autoreactive T cells not Involved In the Initial bout of disease. This may also Involve epltope spreading of disease. Superantigens have also been Implicated In acute diseases such as food poisoning and TSS, and In chronic diseases such as psoriasis and rheumatoid arthritis. Viral superantigens are also Involved In the disease process, Including superantigens derived from human Immunodeficiency virus and mouse mammary tumor virus. Finally, Immunotherapies that ameliorate the role played by superantigens In disease are discussed.

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Section: Immune-based Therapies That Amelioratementioning

confidence: 99%

Superantigens: The Good, the Bad, and the Ugly

Torres

Kominsky

Perrin

et al. 2001

Exp Biol Med (Maywood)

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“…Both RSAD2 and IFIH1 are produced during a viral infection in response to IFNs to limit viral replication and modulate subsequent adaptive immunity (Katze et al 2002, Helbig et al 2005. Similar to other Type I IFNs, IFNT elicits antiviral, antiproliferative, and immunomodulatory activities in homologous and heterologous cells (Pontzer et al 1991, Alexenko et al 1997, Khan et al 1998, 1999b, 1999c, 1999d. Induction of an antiviral state in the endometrium during early pregnancy may be beneficial by inhibiting sexually transmitted viruses as well as modulating local immune cells to promote tolerance of the allogeneic conceptus and stimulating production of cytokines beneficial for conceptus survival and growth (Hansen 1995, Tekin & Hansen 2002, Croy et al 2003b.…”

Section: Introductionmentioning

confidence: 99%

Pregnancy and interferon tau regulate RSAD2 and IFIH1 expression in the ovine uterus

Song¹,

Bazer²,

Spencer³

2007

Reproduction

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Radical S-adenosyl methionine domain containing 2 (RSAD2) encodes a cytoplasmic antiviral protein induced by interferons (IFN). Interferon-induced with helicase C domain 1 (IFIH1) is a RNA helicase involved in innate immune defense against viruses, growth suppression, and apoptosis. Interferon tau (IFNT), a Type I IFN produced by the peri-implantation ruminant conceptus, acts on the uterine endometrium to signal pregnancy recognition and promote receptivity to implantation. Transcriptional profiling identified RSAD2 and IFIH1 as IFNT regulated genes in the ovine uterine endometrium. This study tested the hypothesis that RSAD2 and IFIH1 were induced in the endometrium in a cell type-specific manner by IFNT from the conceptus during early pregnancy. Endometrial RSAD2 and IFIH1 mRNA increased between days 12 and 16 of pregnancy, but not of the estrous cycle. In pregnant ewes, RSAD2 and IFIH1 mRNAs increased in endometrial glands, and stroma and immune cells, but not in the luminal epithelium. Neither gene was expressed in the trophectoderm of day 18 or 20 conceptuses. Progesterone (P4) treatment of ovariectomized ewes did not induce expression RSAD2 or IFIH1 mRNA in the endometrium; however, intrauterine injections of IFNT induced expression of RSAD2 and IFIH1 mRNA in endometria of ewes treated with P4, as well as in ewes treated with P4 and the progesterone receptor antagonist, ZK 136,317. These results indicate that conceptus IFNT induces both RSAD2 and IFIH1 in a P4-independent manner in the ovine uterine endometrium. These two IFNT-stimulated genes are proposed to have biological roles in the establishment of uterine receptivity to the conceptus during implantation through induction of an antiviral state and modulation of local immune cells in the endometrium.

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“…Interferons are cytokines produced by some immune system cells. They possess antiviral, antiseptic, antiproliferative and immunostimulatory activities (Khan et al, 1998;Uematsu & Akira, 2007). Both type I interferons (IFNα and β) and interferon γ have been shown to play a role in the host immune response to cancer (Dunn et al, 2006).…”

Section: Introductionmentioning

confidence: 99%