Therapeutic implications of interferon tau in medicine
Main Article Content
Abstract
Interferon tau has been described as a cytokine associated with the pregnancy recognition signal in ruminants. It is structurally and functionally related to type I interferons and binds to the same receptor, but unlike other interferons, it is not inducible by viruses. Interferon tau is less toxic in vitro and in vivo than interferon alpha and Interferon beta even at high concentrations and displays high species cross-reactivity. This review describes the properties of Interferon tau and its applications in health. We emphasize the antiviral, antiproliferative and anti-inflammatory properties of interferon tau, as well as its effects in mitigating diabetes, obesity, autoimmune diseases, and anti-cancer. Therefore, interferon tau has great potential as a promising therapeutic agent with low cytotoxicity particularly for the treatment of infections and chronic diseases, cancer, and autoimmune disorders with application in health.
Keywords:
Interferon tau, antiviral, immunomodulation, anticancer, diabetes, multiple sclerosis
Article Details
How to Cite
HERNANDEZ TORRES, Erika Itayetzi et al.
Therapeutic implications of interferon tau in medicine.
Medical Research Archives, [S.l.], v. 12, n. 11, nov. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6101>. Date accessed: 12 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i11.6101.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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2. Subramaniam PS, Khan SA, Pontzer CH, Johnson HM. Differential recognition of the type I interferon receptor by interferons tau and alpha is responsible for their disparate cytotoxicities. Proc Natl Acad Sci U S A. 1995;92(26):12270-12274. doi:10.1073/ pnas.92.26.12270
3. Chon TW, Bixler S. Interferon-tau: current applications and potential in antiviral therapy. J Interferon Cytokine Res. 2010;30(7):477-485. doi:10.1089/jir.2009.0089
4. Alexenko AP, Ealy AD, Roberts RM. The cross-species antiviral activities of different IFN-tau subtypes on bovine, murine, and human cells: contradictory evidence for therapeutic potential. J Interferon Cytokine Res. 1999;19(12):1335-1341. doi:10.1089/107999099312795
5. Khan OA, Jiang H, Subramaniam PS, Johnson HM, Dhib-Jalbut SS. Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in multiple sclerosis and autoimmune disorders. Mult Scler. 1998;4(2):63-69. doi:10.1177 /135245859800400204.
6. Bazer FW, Ying W, Wang X, et al. The many faces of interferon tau. Amino Acids. 2015;47 (3):449-460. doi:10.1007/s00726-014-1905-x.
7. Senda T, Saitoh SI, Mitsui Y, Li J, Roberts RM. A three-dimensional model of interferon-tau. J Interferon Cytokine Res. 1995;15(12):1053-1060. doi:10.1089/jir.1995.15.1053.
8. Pontzer CH, Ott TL, Bazer FW, Johnson HM. Structure/function studies with interferon tau: evidence for multiple active sites. J Interferon Res. 1994;14(3):133-141. doi:10.1089/jir.1994.14.133.
9. Brooks K, Spencer TE. Biological roles of interferon tau (IFNT) and type I IFN receptors in elongation of the ovine conceptus. Biol Reprod. 2015;92(2):47. doi:10.1095/biolreprod.114.124156.
10. Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5(5):375-386. doi:10.1038/nri1604.
11. Stewart MD, Johnson GA, Vyhlidal CA, et al. Interferon-tau activates multiple signal transducer and activator of transcription proteins and has complex effects on interferon-responsive gene transcription in ovine endometrial epithelial cells [published correction appears in Endocrinology. 2010 May;151(5):2400. Stewart, D M [corrected to Stewart, M D]. Endocrinology. 2001;142(1):98-107. doi:10.1210/endo.142.1.7891.
12. Fierros-Zárate G, Olvera C, Salazar-Guerrero G, et al. Bovine Interferon-Tau Activates Type I interferon-Associated Janus-signal Transducer in HPV16-positive Tumor Cell. J Cancer. 2020;11(16) :4754-4761. doi:10.7150/jca.33527.
13. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14 (1):36-49. doi:10.1038/nri3581.
14. Mihaescu G, Chifiriuc MC, Filip R, et al. Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection. Front Immunol. 2024;14: 1273604. doi:10.3389/fimmu.2023.1273604.
15. Maneglier B, Rogez-Kreuz C, Dereuddre-Bosquet N, et al. Anti-HIV effects of IFN-tau in human macrophages: role of cellular antiviral factors and interleukin-6. Pathol Biol. 2008; (7-8):492-503. doi: 10.1016/j.patbio.2008.06.002.
16. Pontzer CH, Yamamoto JK, Bazer FW, Ott TL, Johnson HM. Potent anti-feline immunodeficiency virus and anti-human immunodeficiency virus effect of IFN-tau. J Immunol. 1997;158(9):4351-4357.
17. Kohara J, Nishikura Y, Konnai S, Tajima M, Onuma M. Effects of interferon-tau on cattle persistently infected with bovine viral diarrhea virus. Jpn J Vet Res. 2012;60(2-3):63-70.
18. Kohara J, Yokomizo Y. In vitro and in vivo effects of recombinant bovine interferon-tau on bovine leukemia virus. J Vet Med Sci. 2007;69(1): 15-19. doi:10.1292/jvms.69.15.
19. Usharani J, Park SY, Cho EJ, et al. Antiviral activity of ovine interferon tau 4 against foot-and-mouth disease virus. Antiviral Res. 2017; 143:134-141. doi: 10.1016/j.antiviral.2017.01.018.
20. Tennakoon DK, Smith R, Stewart MD, Spencer TE, Nayak M, Welsh CJ. Ovine IFN-tau modulates the expression of MHC antigens on murine cerebrovascular endothelial cells and inhibits replication of Theiler's virus. J Interferon Cytokine Res. 2001;21(10):785-792. doi:10.1089/107999001 753238015.
21. Martín V, Pascual E, Avia M, et al. A Recombinant Adenovirus Expressing Ovine Interferon Tau Prevents Influenza Virus-Induced Lethality in Mice. J Virol. 2016;90(7):3783-3788. doi:10.1128/JVI.03258-15.
22. Juste RA, Ott TL, Kwang J, Bazer FW, de La Concha-Bermejillo A. Effects of recombinant ovine interferon-tau on ovine lentivirus replication and progression of disease. J Gen Virol. 2000;81(Pt 2):525-532. doi:10.1099/0022-1317-81-2-525.
23. Wanjin Tang, Xiaojun Liu, Fuller W Bazer, et al. Interferon Tau Is a Potent Oral Agent against SARS CoV-2 Infection. SM J Infect Dis 2023. 6:12.
24. Johnson JA, Hochkeppel HK, Gangemi JD. IFN-tau exhibits potent suppression of human papillomavirus E6/E7 oncoprotein expression. J Interferon Cytokine Res. 1999;19(10):1107-1116. doi:10.1089/107999099313046.
25. Padilla-Quirarte HO, Trejo-Moreno C, Fierros-Zarate G, et al. Interferon-Tau has Antiproliferative effects, Represses the Expression of E6 and E7 Oncogenes, Induces Apoptosis in Cell Lines Transformed with HPV16 and Inhibits Tumor Growth In Vivo. J Cancer. 2016;7(15):2231-2240. doi:10.7150/jca.15502.
26. Rocha CC, da Silveira JC, Forde N, Binelli M, Pugliesi G. Conceptus-modulated innate immune function during early pregnancy in ruminants: a review. Anim Reprod. 2021;18(1): e20200048. 10. doi:10.1590/1984-3143-AR2020-0048.
27. Rashid NA, Lalitkumar S, Lalitkumar PG, Gemzell-Danielsson K. Endometrial receptivity and human embryo implantation. Am J Reprod Immunol. 2011;66 Suppl 1:23-30. doi:10.1111/j.1 600-0897.2011.01048. x.
28. Binelli M, Subramaniam P, Diaz T, et al. Bovine interferon-tau stimulates the Janus kinase-signal transducer and activator of transcription pathway in bovine endometrial epithelial cells. Biol Reprod. 2001;64(2):654-665. doi:10.1095/biolreprod64.2.654.
29. Spencer TE, Ott TL, Bazer FW. Expression of interferon regulatory factors one and two in the ovine endometrium: effects of pregnancy and ovine interferon tau. Biol Reprod. 1998;58(5):1154-1162. doi:10.1095/biolreprod58.5.1154.
30. Casano AB, Barile VL, Menchetti L, et al. Interferon Tau (IFNt) and Interferon-Stimulated Genes (ISGs) Expression in Peripheral Blood Leukocytes and Correlation with Circulating Pregnancy-Associated Glycoproteins (PAGs) during Peri-Implantation and Early Pregnancy in Buffalo Cows. Animals (Basel). 2022;12(22):3068. doi:10.33 90/ani12223068.
31. Emond V, Asselin É, Fortier MA, Murphy BD, Lambert RD. Interferon-Tau Stimulates Granulocyte-Macrophage Colony-Stimulating Factor Gene Expression in Bovine Lymphocytes and Endometrial Stromal Cells1. Biol Reprod. 2000;62(6):1728-1737 . doi:10.1095/biolreprod62.6.1728.
32. Rooke J, Ewen M, McEvoy T, Entrican G, Ashworth C. Effect of inclusion of serum and granulocyte-macrophage colony stimulating factor on secretion of interferon-tau during the in vitro culture of ovine embryos. Reprod Fertil Dev. 2005;17(5):513-521. doi:10.1071/rd05014.
33. Wicks IP, Roberts AW. Targeting GM-CSF in inflammatory diseases. Nat Rev Rheumatol. 2016;12(1):37-48. doi:10.1038/nrrheum.2015.161.
34. Hara K, Shirasuna K, Usui F, et al. Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages. PLoS One. 2014;9(12): e113974. doi: 10.1371/journal. pone.0113974.
35. Jiang K, Cai J, Jiang Q, et al. Interferon-tau protects bovine endometrial epithelial cells against inflammatory injury by regulating the PI3K/AKT/β-catenin/FoxO1 signaling axis. J Dairy Sci. 2024; 107(1):555-572. doi:10.3168/jds.2022-22983.
36. Zhao G, Wu H, Jiang K, et al. IFN-τ inhibits S. aureus-induced inflammation by suppressing the activation of NF-κB and MAPKs in RAW 264.7 cells and mice with pneumonia. Int Immunopharmacol. 2016; 35:332-340. doi: 10.1016/j.intimp.2016.02.016.
37. Chon TW, Bixler S. Interferon-tau: current applications and potential in antiviral therapy. J Interferon Cytokine Res. 2010;30(7):477-485. doi:10.1089/jir.2009.0089.
38. Li J, Roberts RM. Structure-function relationships in the interferon-tau (IFN-tau). Changes in receptor binding and in antiviral and antiproliferative activities resulting from site-directed mutagenesis performed near the carboxyl terminus. J Biol Chem. 1994;269(40):24826-24833.
39. Suzuki T, Sakumoto R, Hayashi KG, et al. Involvement of interferon-tau in the induction of apoptotic, pyroptotic, and autophagic cell death-related signaling pathways in the bovine uterine endometrium during early pregnancy. J Reprod Dev. 2018;64(6):495-502. doi:10.1262/jrd.2018-063.
40. Subramaniam PS, Johnson HM. A role for the cyclin-dependent kinase inhibitor p21 in the G1 cell cycle arrest mediated by the type I interferons. J Interferon Cytokine Res. 1997;17(1):11-15. doi:10.1089/jir.1997.17.11.
41. Johnson JA, Hochkeppel HK, Gangemi JD. IFN-tau exhibits potent suppression of human papillomavirus E6/E7 oncoprotein expression. J Interferon Cytokine Res. 1999;19(10):1107-1116. doi:10.1089/107999099313046.
42. Espin-Rivera AM, Meza-Aparicio FU, Reyna-Flores F, Burguete-Garcia AI, Guzman-Olea E, Bermudez-Morales VH. Interferon-tau (IFN-τ) Has Antiproliferative Effects, Induces Apoptosis, and Inhibits Tumor Growth in a Triple-negative Breast Cancer Murine Tumor Model. In Vivo. 2023;37 (6):2517-2523. doi:10.21873/invivo.13359.
43. Ren W, Chen S, Zhang L, et al. Interferon Tau Affects Mouse Intestinal Microbiota and Expression of IL-17. Mediators Inflamm. 2016; 2016:2839232. doi:10.1155/2016/2839232.
44. Xue G, Zheng Z, Liang X, Zheng Y, Wu H. Uterine Tissue Metabonomics Combined with 16S rRNA Gene Sequencing to Analyze the Changes of Gut Microbiota in Mice with Endometritis and the Intervention Effect of Tau Interferon. Microbiol Spectr. 2023;11(3): e0040923. doi:10.1128/spectrum.00409-23.
45. Sobel DO, Ahvazi B, Amjad F, Mitnaul L, Pontzer C. Interferon-tau inhibits the development of diabetes in NOD mice. Autoimmunity. 2008; 41(7):543-553. doi:10.1080/08916930802194195.
46. Ying W, Kanameni S, Chang CA, et al. Interferon tau alleviates obesity-induced adipose tissue inflammation and insulin resistance by regulating macrophage polarization. PLoS One. 2014;9(6): e98835. doi: 10.1371/journal.pone.0098835.
47. Reder AT, Feng X. How type I interferons work in multiple sclerosis and other diseases: some unexpected mechanisms. J Interferon Cytokine Res. 2014;34(8):589-599. doi:10.1089/jir.2013.0158.
48. NIH 2004 Oral IFN-tau treatment in RRMS patients | www.inknowvation.com. Home | www.inknowvation.com. Accessed on September 21, 2024. https://www.inknowvation.com/sbir/awards/nih-2004-oral-ifn-tau-treatment-rrms-patients
49. Find and participate in clinical trials and research studies happening around the world | TrialScreen. Find and participate in clinical trials and research studies happening around the world | TrialScreen. Accessed on September 21, 2024. https://app.trialscreen.org/trials/phase-2-multiple-sclerosis-safety-efficacy-oral-ifn-tau-patients-relapsing-trial-actrn12606000241538
50. Lorelie V. Oral IFN-tau treatment in RRMS patients. Grantome. March 1, 2004. Accessed September 21, 2024. https://grantome.com/grant/NIH/R43-AI055227-01A1.
2. Subramaniam PS, Khan SA, Pontzer CH, Johnson HM. Differential recognition of the type I interferon receptor by interferons tau and alpha is responsible for their disparate cytotoxicities. Proc Natl Acad Sci U S A. 1995;92(26):12270-12274. doi:10.1073/ pnas.92.26.12270
3. Chon TW, Bixler S. Interferon-tau: current applications and potential in antiviral therapy. J Interferon Cytokine Res. 2010;30(7):477-485. doi:10.1089/jir.2009.0089
4. Alexenko AP, Ealy AD, Roberts RM. The cross-species antiviral activities of different IFN-tau subtypes on bovine, murine, and human cells: contradictory evidence for therapeutic potential. J Interferon Cytokine Res. 1999;19(12):1335-1341. doi:10.1089/107999099312795
5. Khan OA, Jiang H, Subramaniam PS, Johnson HM, Dhib-Jalbut SS. Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in multiple sclerosis and autoimmune disorders. Mult Scler. 1998;4(2):63-69. doi:10.1177 /135245859800400204.
6. Bazer FW, Ying W, Wang X, et al. The many faces of interferon tau. Amino Acids. 2015;47 (3):449-460. doi:10.1007/s00726-014-1905-x.
7. Senda T, Saitoh SI, Mitsui Y, Li J, Roberts RM. A three-dimensional model of interferon-tau. J Interferon Cytokine Res. 1995;15(12):1053-1060. doi:10.1089/jir.1995.15.1053.
8. Pontzer CH, Ott TL, Bazer FW, Johnson HM. Structure/function studies with interferon tau: evidence for multiple active sites. J Interferon Res. 1994;14(3):133-141. doi:10.1089/jir.1994.14.133.
9. Brooks K, Spencer TE. Biological roles of interferon tau (IFNT) and type I IFN receptors in elongation of the ovine conceptus. Biol Reprod. 2015;92(2):47. doi:10.1095/biolreprod.114.124156.
10. Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5(5):375-386. doi:10.1038/nri1604.
11. Stewart MD, Johnson GA, Vyhlidal CA, et al. Interferon-tau activates multiple signal transducer and activator of transcription proteins and has complex effects on interferon-responsive gene transcription in ovine endometrial epithelial cells [published correction appears in Endocrinology. 2010 May;151(5):2400. Stewart, D M [corrected to Stewart, M D]. Endocrinology. 2001;142(1):98-107. doi:10.1210/endo.142.1.7891.
12. Fierros-Zárate G, Olvera C, Salazar-Guerrero G, et al. Bovine Interferon-Tau Activates Type I interferon-Associated Janus-signal Transducer in HPV16-positive Tumor Cell. J Cancer. 2020;11(16) :4754-4761. doi:10.7150/jca.33527.
13. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14 (1):36-49. doi:10.1038/nri3581.
14. Mihaescu G, Chifiriuc MC, Filip R, et al. Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection. Front Immunol. 2024;14: 1273604. doi:10.3389/fimmu.2023.1273604.
15. Maneglier B, Rogez-Kreuz C, Dereuddre-Bosquet N, et al. Anti-HIV effects of IFN-tau in human macrophages: role of cellular antiviral factors and interleukin-6. Pathol Biol. 2008; (7-8):492-503. doi: 10.1016/j.patbio.2008.06.002.
16. Pontzer CH, Yamamoto JK, Bazer FW, Ott TL, Johnson HM. Potent anti-feline immunodeficiency virus and anti-human immunodeficiency virus effect of IFN-tau. J Immunol. 1997;158(9):4351-4357.
17. Kohara J, Nishikura Y, Konnai S, Tajima M, Onuma M. Effects of interferon-tau on cattle persistently infected with bovine viral diarrhea virus. Jpn J Vet Res. 2012;60(2-3):63-70.
18. Kohara J, Yokomizo Y. In vitro and in vivo effects of recombinant bovine interferon-tau on bovine leukemia virus. J Vet Med Sci. 2007;69(1): 15-19. doi:10.1292/jvms.69.15.
19. Usharani J, Park SY, Cho EJ, et al. Antiviral activity of ovine interferon tau 4 against foot-and-mouth disease virus. Antiviral Res. 2017; 143:134-141. doi: 10.1016/j.antiviral.2017.01.018.
20. Tennakoon DK, Smith R, Stewart MD, Spencer TE, Nayak M, Welsh CJ. Ovine IFN-tau modulates the expression of MHC antigens on murine cerebrovascular endothelial cells and inhibits replication of Theiler's virus. J Interferon Cytokine Res. 2001;21(10):785-792. doi:10.1089/107999001 753238015.
21. Martín V, Pascual E, Avia M, et al. A Recombinant Adenovirus Expressing Ovine Interferon Tau Prevents Influenza Virus-Induced Lethality in Mice. J Virol. 2016;90(7):3783-3788. doi:10.1128/JVI.03258-15.
22. Juste RA, Ott TL, Kwang J, Bazer FW, de La Concha-Bermejillo A. Effects of recombinant ovine interferon-tau on ovine lentivirus replication and progression of disease. J Gen Virol. 2000;81(Pt 2):525-532. doi:10.1099/0022-1317-81-2-525.
23. Wanjin Tang, Xiaojun Liu, Fuller W Bazer, et al. Interferon Tau Is a Potent Oral Agent against SARS CoV-2 Infection. SM J Infect Dis 2023. 6:12.
24. Johnson JA, Hochkeppel HK, Gangemi JD. IFN-tau exhibits potent suppression of human papillomavirus E6/E7 oncoprotein expression. J Interferon Cytokine Res. 1999;19(10):1107-1116. doi:10.1089/107999099313046.
25. Padilla-Quirarte HO, Trejo-Moreno C, Fierros-Zarate G, et al. Interferon-Tau has Antiproliferative effects, Represses the Expression of E6 and E7 Oncogenes, Induces Apoptosis in Cell Lines Transformed with HPV16 and Inhibits Tumor Growth In Vivo. J Cancer. 2016;7(15):2231-2240. doi:10.7150/jca.15502.
26. Rocha CC, da Silveira JC, Forde N, Binelli M, Pugliesi G. Conceptus-modulated innate immune function during early pregnancy in ruminants: a review. Anim Reprod. 2021;18(1): e20200048. 10. doi:10.1590/1984-3143-AR2020-0048.
27. Rashid NA, Lalitkumar S, Lalitkumar PG, Gemzell-Danielsson K. Endometrial receptivity and human embryo implantation. Am J Reprod Immunol. 2011;66 Suppl 1:23-30. doi:10.1111/j.1 600-0897.2011.01048. x.
28. Binelli M, Subramaniam P, Diaz T, et al. Bovine interferon-tau stimulates the Janus kinase-signal transducer and activator of transcription pathway in bovine endometrial epithelial cells. Biol Reprod. 2001;64(2):654-665. doi:10.1095/biolreprod64.2.654.
29. Spencer TE, Ott TL, Bazer FW. Expression of interferon regulatory factors one and two in the ovine endometrium: effects of pregnancy and ovine interferon tau. Biol Reprod. 1998;58(5):1154-1162. doi:10.1095/biolreprod58.5.1154.
30. Casano AB, Barile VL, Menchetti L, et al. Interferon Tau (IFNt) and Interferon-Stimulated Genes (ISGs) Expression in Peripheral Blood Leukocytes and Correlation with Circulating Pregnancy-Associated Glycoproteins (PAGs) during Peri-Implantation and Early Pregnancy in Buffalo Cows. Animals (Basel). 2022;12(22):3068. doi:10.33 90/ani12223068.
31. Emond V, Asselin É, Fortier MA, Murphy BD, Lambert RD. Interferon-Tau Stimulates Granulocyte-Macrophage Colony-Stimulating Factor Gene Expression in Bovine Lymphocytes and Endometrial Stromal Cells1. Biol Reprod. 2000;62(6):1728-1737 . doi:10.1095/biolreprod62.6.1728.
32. Rooke J, Ewen M, McEvoy T, Entrican G, Ashworth C. Effect of inclusion of serum and granulocyte-macrophage colony stimulating factor on secretion of interferon-tau during the in vitro culture of ovine embryos. Reprod Fertil Dev. 2005;17(5):513-521. doi:10.1071/rd05014.
33. Wicks IP, Roberts AW. Targeting GM-CSF in inflammatory diseases. Nat Rev Rheumatol. 2016;12(1):37-48. doi:10.1038/nrrheum.2015.161.
34. Hara K, Shirasuna K, Usui F, et al. Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages. PLoS One. 2014;9(12): e113974. doi: 10.1371/journal. pone.0113974.
35. Jiang K, Cai J, Jiang Q, et al. Interferon-tau protects bovine endometrial epithelial cells against inflammatory injury by regulating the PI3K/AKT/β-catenin/FoxO1 signaling axis. J Dairy Sci. 2024; 107(1):555-572. doi:10.3168/jds.2022-22983.
36. Zhao G, Wu H, Jiang K, et al. IFN-τ inhibits S. aureus-induced inflammation by suppressing the activation of NF-κB and MAPKs in RAW 264.7 cells and mice with pneumonia. Int Immunopharmacol. 2016; 35:332-340. doi: 10.1016/j.intimp.2016.02.016.
37. Chon TW, Bixler S. Interferon-tau: current applications and potential in antiviral therapy. J Interferon Cytokine Res. 2010;30(7):477-485. doi:10.1089/jir.2009.0089.
38. Li J, Roberts RM. Structure-function relationships in the interferon-tau (IFN-tau). Changes in receptor binding and in antiviral and antiproliferative activities resulting from site-directed mutagenesis performed near the carboxyl terminus. J Biol Chem. 1994;269(40):24826-24833.
39. Suzuki T, Sakumoto R, Hayashi KG, et al. Involvement of interferon-tau in the induction of apoptotic, pyroptotic, and autophagic cell death-related signaling pathways in the bovine uterine endometrium during early pregnancy. J Reprod Dev. 2018;64(6):495-502. doi:10.1262/jrd.2018-063.
40. Subramaniam PS, Johnson HM. A role for the cyclin-dependent kinase inhibitor p21 in the G1 cell cycle arrest mediated by the type I interferons. J Interferon Cytokine Res. 1997;17(1):11-15. doi:10.1089/jir.1997.17.11.
41. Johnson JA, Hochkeppel HK, Gangemi JD. IFN-tau exhibits potent suppression of human papillomavirus E6/E7 oncoprotein expression. J Interferon Cytokine Res. 1999;19(10):1107-1116. doi:10.1089/107999099313046.
42. Espin-Rivera AM, Meza-Aparicio FU, Reyna-Flores F, Burguete-Garcia AI, Guzman-Olea E, Bermudez-Morales VH. Interferon-tau (IFN-τ) Has Antiproliferative Effects, Induces Apoptosis, and Inhibits Tumor Growth in a Triple-negative Breast Cancer Murine Tumor Model. In Vivo. 2023;37 (6):2517-2523. doi:10.21873/invivo.13359.
43. Ren W, Chen S, Zhang L, et al. Interferon Tau Affects Mouse Intestinal Microbiota and Expression of IL-17. Mediators Inflamm. 2016; 2016:2839232. doi:10.1155/2016/2839232.
44. Xue G, Zheng Z, Liang X, Zheng Y, Wu H. Uterine Tissue Metabonomics Combined with 16S rRNA Gene Sequencing to Analyze the Changes of Gut Microbiota in Mice with Endometritis and the Intervention Effect of Tau Interferon. Microbiol Spectr. 2023;11(3): e0040923. doi:10.1128/spectrum.00409-23.
45. Sobel DO, Ahvazi B, Amjad F, Mitnaul L, Pontzer C. Interferon-tau inhibits the development of diabetes in NOD mice. Autoimmunity. 2008; 41(7):543-553. doi:10.1080/08916930802194195.
46. Ying W, Kanameni S, Chang CA, et al. Interferon tau alleviates obesity-induced adipose tissue inflammation and insulin resistance by regulating macrophage polarization. PLoS One. 2014;9(6): e98835. doi: 10.1371/journal.pone.0098835.
47. Reder AT, Feng X. How type I interferons work in multiple sclerosis and other diseases: some unexpected mechanisms. J Interferon Cytokine Res. 2014;34(8):589-599. doi:10.1089/jir.2013.0158.
48. NIH 2004 Oral IFN-tau treatment in RRMS patients | www.inknowvation.com. Home | www.inknowvation.com. Accessed on September 21, 2024. https://www.inknowvation.com/sbir/awards/nih-2004-oral-ifn-tau-treatment-rrms-patients
49. Find and participate in clinical trials and research studies happening around the world | TrialScreen. Find and participate in clinical trials and research studies happening around the world | TrialScreen. Accessed on September 21, 2024. https://app.trialscreen.org/trials/phase-2-multiple-sclerosis-safety-efficacy-oral-ifn-tau-patients-relapsing-trial-actrn12606000241538
50. Lorelie V. Oral IFN-tau treatment in RRMS patients. Grantome. March 1, 2004. Accessed September 21, 2024. https://grantome.com/grant/NIH/R43-AI055227-01A1.