Ebi3-KO Mouse

Ebi3, or Epstein-Barr virus-induced gene 3, is a β subunit within the IL-12 cytokine family. It canonically binds to α subunits p19, p28, or p35 to form heterodimeric cytokines IL-39, IL-27, and IL-35 respectively, playing critical roles in regulating immune responses, inflammation, and cell differentiation [2,3]. Ebi3 can also bind to other cytokines like IFN-γ and IL-10, affecting their signal transduction and downstream functions [2]. Additionally, it has a chaperone-like role in promoting the proper folding of target proteins in collaboration with calnexin under inflammatory conditions [3].

In Ebi3 knockout (KO) mouse models, Ebi3 deficiency was found to exacerbate experimental periodontitis. The KO mice showed more intense alveolar bone resorption, higher IL-17A expression, and lower IL-10 expression in the gingiva compared to wild-type mice. Recombinant IL-35 injection could alleviate the alveolar bone resorption in Ebi3 KO mice, suggesting Th17 cells exacerbate experimental periodontitis in Ebi3-deficient mice and IL-35 may inhibit periodontal tissue destruction [1]. In another study, Ebi3-deficient C57BL/6 mice infected with mouse cytomegalovirus (MCMV) showed decreased viral load in salivary glands and oral lavage, along with a decrease in sustained IL-10 production by NK cells and an increase in dendritic cell maturation markers and activated CD8+ T cells, indicating Ebi3 dampens the immune response against MCMV infection and is involved in MCMV latency establishment [4].

In conclusion, Ebi3 is crucial in regulating immune and inflammatory responses. The Ebi3 KO mouse models have revealed its role in diseases such as experimental periodontitis and MCMV-related immune regulation, enhancing our understanding of its functions in specific disease contexts.

References:

1. Goto, Hisashi, Kikuchi, Takeshi, Takayanagi, Yuhei, Hayashi, Jun-Ichiro, Mitani, Akio. 2023. Ebi3 knockout aggravates experimental periodontitis via Th17 polarization. In Journal of clinical periodontology, 50, 1406-1418. doi:10.1111/jcpe.13859. https://pubmed.ncbi.nlm.nih.gov/37534736/

2. Scott, Ellen N, Ye, Cheng, Yano, Hiroshi, Workman, Creg J, Vignali, Dario A A. . Ebi3 Binding to IFN-γ and IL-10 Limits Their Function. In Journal of immunology (Baltimore, Md. : 1950), 213, 1115-1124. doi:10.4049/jimmunol.2400236. https://pubmed.ncbi.nlm.nih.gov/39240167/

3. Watanabe, Aruma, Mizoguchi, Izuru, Hasegawa, Hideaki, Yoneto, Toshihiko, Yoshimoto, Takayuki. 2021. A Chaperone-Like Role for EBI3 in Collaboration With Calnexin Under Inflammatory Conditions. In Frontiers in immunology, 12, 757669. doi:10.3389/fimmu.2021.757669. https://pubmed.ncbi.nlm.nih.gov/34603342/

4. Jensen, Helle, Chen, Shih-Yu, Folkersen, Lasse, Nolan, Garry P, Lanier, Lewis L. 2017. EBI3 regulates the NK cell response to mouse cytomegalovirus infection. In Proceedings of the National Academy of Sciences of the United States of America, 114, 1625-1630. doi:10.1073/pnas.1700231114. https://pubmed.ncbi.nlm.nih.gov/28143936/