Eomes, short for Eomesodermin, is a transcription factor that plays crucial roles in the development and function of various immune cells. It is involved in pathways related to immune cell differentiation, activation, and function, being of great biological importance in the immune system. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying Eomes [1,2,3,4,5,6].

In NK cell development, EomeshiNKneg cells expressing Eomes in the bone marrow are identified as precursors to classical NK cells, demonstrating an early divergence of NK and ILC1 lineages [1]. In CD8+ T cells, Eomes shows tissue-specific roles; it supports the maintenance of established tissue-resident memory CD8+ T (TRM) cells in the small intestine but not in the colon [2]. Deletion of Eomes in antigen-specific CD4+ T cells protects against CNS inflammation, as Eomes is required for the long-term maintenance of CNS-infiltrating CD4+ T cells through regulating mitochondrial functions [3]. Also, deletion of T-BET and EOMES in unexpanded primary human NK cells compromises in vivo antitumor response, normal proliferation, and persistence of NK cells, along with defective cytokine responses [4]. Moreover, in CD8+ T cells within the tumor microenvironment, Eomes-dependent loss of the co-activating receptor CD226 restrains anti-tumor functions and limits cancer immunotherapy efficacy [5].

In conclusion, Eomes is essential for the development, function, and maintenance of multiple immune cell types. Model-based research, especially KO/CKO mouse models, has revealed its significant contributions in diseases related to immune-mediated inflammation, such as multiple sclerosis, and in cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Liang, Zhitao, Anderson, Hope D, Locher, Veronica, McDonald, Benjamin D, Bendelac, Albert. 2024. Eomes expression identifies the early bone marrow precursor to classical NK cells. In Nature immunology, 25, 1172-1182. doi:10.1038/s41590-024-01861-6. https://pubmed.ncbi.nlm.nih.gov/38871999/

2. Lin, Yun Hsuan, Duong, Han G, Limary, Abigail E, Goldrath, Ananda W, Chang, John T. 2022. Small intestine and colon tissue-resident memory CD8+ T cells exhibit molecular heterogeneity and differential dependence on Eomes. In Immunity, 56, 207-223.e8. doi:10.1016/j.immuni.2022.12.007. https://pubmed.ncbi.nlm.nih.gov/36580919/

3. Joulia, Emeline, Michieletto, Michaël F, Agesta, Arantxa, Sarry, Jean-Emmanuel, Dejean, Anne S. 2024. Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation. In The Journal of experimental medicine, 221, . doi:10.1084/jem.20230449. https://pubmed.ncbi.nlm.nih.gov/38189779/

4. Wong, Pamela, Foltz, Jennifer A, Chang, Lily, Berrien-Elliott, Melissa M, Fehniger, Todd A. 2023. T-BET and EOMES sustain mature human NK cell identity and antitumor function. In The Journal of clinical investigation, 133, . doi:10.1172/JCI162530. https://pubmed.ncbi.nlm.nih.gov/37279078/

5. Weulersse, Marianne, Asrir, Assia, Pichler, Andrea C, Smyth, Mark J, Martinet, Ludovic. . Eomes-Dependent Loss of the Co-activating Receptor CD226 Restrains CD8+ T Cell Anti-tumor Functions and Limits the Efficacy of Cancer Immunotherapy. In Immunity, 53, 824-839.e10. doi:10.1016/j.immuni.2020.09.006. https://pubmed.ncbi.nlm.nih.gov/33053331/

6. Liao, Yue, Zheng, Yanling, Zhang, Ruizhi, Li, Xiaomin, Shen, Erxia. 2024. Regulatory roles of transcription factors T-bet and Eomes in group 1 ILCs. In International immunopharmacology, 143, 113229. doi:10.1016/j.intimp.2024.113229. https://pubmed.ncbi.nlm.nih.gov/39357208/