Ifne, also known as interferon epsilon, is a cytokine belonging to the interferon family. It is constitutively expressed in the epithelium of the female reproductive tract and plays a vital role in protecting against sexually transmitted pathogens. IFN-ε may modulate immunological functions, and its inflammation-modulating functions might be related to the pathophysiology of certain diseases [1,4].

In gene-related functional studies, IFN-ε-deficient mice showed increased susceptibility to vaginal Zika virus (ZIKV) infection, indicating IFN-ε's critical role in host protection against vaginal ZIKV infection [3]. Intravaginal administration of recombinant IFN-ε protected Ifnɛ-/-mice and highly susceptible Ifnar1-/-mice against vaginal ZIKV infection, suggesting IFN-ε can provide protection even without signals from other type-I IFNs and in an IFNAR1-independent manner [3]. In high-risk human papillomavirus (HR-HPV) infections, the mRNA expression of IFN-ε was higher in the ectocervix than other IFNs and was further upregulated in HR-HPV positive women compared with negative ones, though the protein expression was comparable between infected patients and healthy controls [1]. In condyloma acuminata, IFN-ε was markedly upregulated in CA warts and HPV-infected keratinocytes and suppressed the susceptibility of HPV infection directly [2].

In conclusion, Ifne is crucial for protecting the female reproductive tract against sexually transmitted viral infections like ZIKV and HPV. Gene knockout mouse models, such as IFN-ε-deficient mice, have revealed its important role in host defense mechanisms in the female reproductive tract, providing insights into the innate immune response to these infections and potential new therapeutic approaches for related diseases.

References:

1. Zhang, Lu, Zhou, Yuechen, Xing, Xiaoyan, Qian, Ruiya, Hu, Xiaoyu. . Upregulation of IFNE in cervical biopsies of patients with high-risk human papillomavirus infections. In Immunity, inflammation and disease, 11, e1111. doi:10.1002/iid3.1111. https://pubmed.ncbi.nlm.nih.gov/38156399/

2. Gu, Zhichao, Liu, Jiaying, Qin, Lei, Cao, Yuchun, Zhang, Huafeng. 2023. WTAP-mediated m6A modification of IFNE is required for antiviral defense in condyloma acuminata. In Journal of dermatological science, 111, 43-51. doi:10.1016/j.jdermsci.2023.07.004. https://pubmed.ncbi.nlm.nih.gov/37516644/

3. Xu, Chuan, Wang, Annie, Ebraham, Laith, Beaulieu, Aimee, Chang, Theresa L. 2023. Interferon ɛ restricts Zika virus infection in the female reproductive tract. In PNAS nexus, 2, pgad350. doi:10.1093/pnasnexus/pgad350. https://pubmed.ncbi.nlm.nih.gov/37954158/

4. Cho, Hee-Ryung, Kim, Su Kang, Lim, Hee-Kyeong, Chung, Joo-Ho, Lee, Mu-Hyoung. . Association study between nonsense polymorphism (rs2039381, Gln71Stop) of interferon-ε and susceptibility to vitiligo in Korean population. In Immunological investigations, 42, 423-30. doi:10.3109/08820139.2013.804836. https://pubmed.ncbi.nlm.nih.gov/23802172/