Recent progress of interferon-tau research and potential direction beyond pregnancy recognition

Bai, Hanako; Kawahara, Manabu; Takahashi, Masashi; Imakawa, Kazuhiko

doi:10.1262/jrd.2022-061

Cited by 10 publications

(5 citation statements)

References 118 publications

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“…Given results from NCT data, there is a high number of reasons to believe that lowdose type IFN I and III IFN based nasal sprays could match the definition of a therapeutic vaccine with beneficial effects than prophylactic ones.Therefore, whilst potential vaccine candidates can prevent severe cases of COVID-19 disease, it would have the highest impact when administered in varying populations of vulnerable people potentially with or without comorbidities who became infected and developed symptoms that would be noticeable . Examining further the administration of type I IFN from NCTs clarifies that IFN alpha-2b, epsilon, omega and perhaps IFN beta1, (BAI et al, 2022) and type III (IFN lambda1, lambda2 and lambda3) may act as mimitics of cellular infection and stimulate a robust and natural immune response against either viral or neoplastic pathologies, and likewise, such an intervention fits the definition of a traditional vaccine. Because this likely requires further research into dosages, we might refer to the potential immunization process as a long-term one.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Interferon I and III-Based Nasal Sprays: A Good-Looking COVID-19 Vaccine Candidate and a Therapy of the Future?

Carp¹,

Metoudi²,

Brown³

et al. 2023

Preprint

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The SARS–CoV-2 infection has caused both acute and chronic COVID–19 disease during the recent pandemic with emerging more transmissible SARS–CoV–2 Omicron variants (BQ1 and XBB1) that have increased demands for more effective immunogens and therapeutic approaches to protect the lives of numerous SARS–CoV-2 affected individuals and reduce overall disease burden that could be affected by concurrent other pathogens causing diseases. Following a worldwide campaign of mass vaccination, there is still a significant demand to quell the harmful effects of novel SARS–CoV–2 infections due to higher mutation rates within specific areas of the SARS–CoV-2 domain, leading to enhanced viral entry, especially within individuals with one or more significant comorbidities, and there is still a dilemma of how prevention of future pandemics will occur as within host animal mutations and cross species transfer naturally occurs. Concerns intersect at a specific point; a gained evolutionary ability of several viruses over the previous centuries to remain undetected during the first stages of infection by means of capping the 5' end of their DNA and RNA genes respectively. This may occur by reducing the rate of host Type I and Type III Interferons (IFN) cellular synthesis, that would usually occur and affect both apoptotic pathways, that facilitate viral replication and clearance, as well as immune cells, that process and present pathogenic antigen epitopes. Furthermore, although methods of vaccination exist, other methods in clinical development remain that could evoke an immune response in different cellular, serum or mucosal compartments being cellular, serum and mucosal that evoke differential antibody responses. Antibodies are classed as natural and synthetic. Natural antibodies are further classified into neutralizing and non-neutralizing, whilst synthetic antibodies are also further classified into monoclonal and polyclonal. As a result of single cell study transcriptome research, viruses do utilize an array of protein receptors for receptor-mediated cellular entry. This, therefore suggests that potential differential production of antibody immunoglobulins (Ig) within serum and mucosal areas remains affected by cytokines, adhesion molecules and chemokines that can be upregulated or downregulated upon host viral infection. Serum plasma antibodies can be multimeric that may not efficiently cross the nasal epithelium cell layer, therefore offering less protection against mucosal inflammation due to mucin proteins. On the other hand, antibodies produced by mucosal plasma cells at epithelial surfaces are known to provide effective immune responses in some viral infections. The existence of developments that stimulate mucosal immune responses has so far only been seen with influenza nasal immunogens. Nevertheless, scientists developed ways of immunization and early treatment worldwide that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration. For example, the administration of human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can stimulate cellular activity to train the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Recently, it was discovered that specific plants secrete proteins that also stimulate the production of Type I Interferons. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. Naturally-selected polymorphic viruses through genetic recombination pose challenges to traditional concepts of cellular and molecular immune system neutralization of these viruses during the first stages of cellular infection. It is until the scientific community realizes this potentially crucial aspect that we will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently monkeypox. Type I IFNs tend to be produced faster than Type III IFNs, and the first induce slightly more abundant pro-inflammatory signals than the latter, meaning that type III IFNs, if produced early, may further decrease the extent of excessive proinflammatory signals. Hence, we believe that nasal sprays containing a low dosage of Type I and Type III IFNs not only represent a relevant COVID-19 therapeutic, but also a potential unknown modulatory therapy of the future. Of note, it has been indicated that IFN I and / or III display significant immunizing and early therapeutic effects for other viral evoked diseases like Influenza (Influenza (A)H1N1), rabies (Rabies lyssavirus), measles (Measles virus), rubella (Rubivirus rubellae), Hepatitis B, HIV-induced AIDS, Ebola, Marburg, as well as bacterial diseases, such as lower respiratory tract infectious diseases induced by Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus, and a number of oncological diseases, like hepatic melanoma.

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Section: Discussionmentioning

confidence: 99%

Low-Dose Interferon I and III-Based Nasal Sprays: A Good-Looking COVID-19 Vaccine Candidate and a Therapy of the Future?

Carp¹,

Metoudi²,

Brown³

et al. 2023

Preprint

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“…On gestational days 14-15 in cattle, the elongating conceptus begins to produce a major cytokine, IFNT, which peaks on day 19 and declines soon after the conceptus attaches to the uterine epithelium. IFNT, a pregnancy recognition protein, acts on the expression of elongation-and implantation-related genes in the endometrium and abrogates luteolytic mechanisms, leading to continued P4 production [27,28]. Recent studies on ovine and bovine EVs have shown that uterine EVs contained IFNT [20,29,30] and upregulated the expression of several IFNT-stimulated genes (ISGs), such as ISG15, MX1, MX2, STAT1, and STAT2 in EECs during the peri-attachment period [20,30].…”

Section: Discussionmentioning

confidence: 99%

Global analyses and potential effects of extracellular vesicles on the establishment of conceptus implantation during the peri-implantation period

Nakamura

Kusama

Hori

et al. 2023

Journal of Reproduction and Development

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Intrauterine extracellular vesicles (EVs) are involved in establishing proper conceptus-endometrial communication, which is essential for conceptus implantation and subsequent successful placentation.Despite several studies on intrauterine EVs, the composition and quantitative changes in conceptus and endometrial EVs, as well as the effects of intrauterine EVs on endometrial epithelial cells (EECs) during the peri-implantation period, have not been well characterized. To elucidate global changes in proteins in EVs extracted from uterine flushings (UFs) during the pre-implantation (P17), just-implantation (P20), and post-implantation (P22) periods, the datasets of the proteome iTRAQ analysis were compared among P17, P20, and P22 EVs. These analyses revealed that the composition and function of proteins in the EVs changed dramatically during peri-implantation in cattle. Notably, intrauterine P17 EVs affected the high expression of "Developmental Biology" and "morphogenesis of an endothelium" compared with those in P20 and P22 EVs. Furthermore, P20 EVs had the functions of the high expression of "mitochondrial calcium ion homeostasis" and "Viral mRNA Translation" compared with those in P17 EVs. Transcripts extracted from EECs treated with P17, P20, or P22 EVs were subjected to RNA-seq analysis. These analyses identified 60 transcripts in EECs commonly induced by intrauterine EVs recovered from P17, P20, and P22, a large number of which were associated with "type I interferon signaling pathway." Collectively, these findings reveal the presence and multiple functions of EVs that are potentially implicated in facilitating conceptus implantation into the uterine epithelium during the peri-implantation period.

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“…The IFNT, which is present at low levels in extrauterine tissues as well as the peripheral circulation, signals the maternal recognition of bovine pregnancy (Szenci, 2021). IFNT helps maintain the corpus luteum function and regulates the maternal immune system to ensure embryo implantation (Bai et al, 2022;Martal et al, 1990;Talukder et al, 2017). IFNT has been shown to act in a paracrine manner on the endometrium by inhibiting the secretion of prostaglandin F2α (PGF2α), which prevents the lysis of the corpus luteum, ensuring that the ovarian corpus luteum continues to produce progesterone (Spencer et al, 2007;Wiltbank et al, 2023).…”

Section: Ifnt and Isg Smentioning

confidence: 99%

Recent advances in early pregnancy loss diagnosis in dairy cows: New approaches

Gui,

Dai,

Guo

et al. 2024

Reprod Domestic Animals

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Early pregnancy loss is a primary cause of low reproductive rates in dairy cows, posing severe economic losses to dairy farming. The accurate diagnosis of dairy cows with early pregnancy loss allows for oestrus synchronization, shortening day open, and increasing the overall conception rate of the herd. Several techniques are available for detecting early pregnancy loss in dairy cows, including rectal ultrasound, circulating blood progesterone, and pregnancy‐associated glycoproteins (PAGs). Yet, there is a need to improve on existing techniques and develop novel strategies to identify cows with early pregnancy loss accurately. This manuscript reviews the applications of rectal ultrasound, circulating blood progesterone concentration, and PAGs in the diagnosis of pregnancy loss in dairy cows. The manuscript also discusses the recent progress of new technologies, including colour Doppler ultrasound (CDUS), interferon tau‐induced genes (ISGs), and exosomal miRNA in diagnosing pregnancy loss in dairy cows. This study will provide an option for producers to re‐breed cows with pregnancy loss, thereby reducing the calving interval and economic costs. Meanwhile, this manuscript might also act as a reference for exploring more economical and precise diagnostic technologies for early pregnancy loss in dairy cows.

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Recent progress of interferon-tau research and potential direction beyond pregnancy recognition

Cited by 10 publications

References 118 publications

Low-Dose Interferon I and III-Based Nasal Sprays: A Good-Looking COVID-19 Vaccine Candidate and a Therapy of the Future?

Low-Dose Interferon I and III-Based Nasal Sprays: A Good-Looking COVID-19 Vaccine Candidate and a Therapy of the Future?

Global analyses and potential effects of extracellular vesicles on the establishment of conceptus implantation during the peri-implantation period

Recent advances in early pregnancy loss diagnosis in dairy cows: New approaches

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