Eomes, also known as Eomesodermin, is a transcription factor that plays crucial roles in the development and function of various immune cells and in early embryonic development. In the immune system, it is involved in the differentiation and functional maintenance of natural killer (NK) cells, type 1 innate lymphoid cells (ILC1s), CD8+ T cells, and CD4+ T cells, and is associated with pathways related to immune responses against infections and tumors. In embryonic development, it participates in the specification of mesoderm and definitive endoderm [1,2,3,4,6,7]. Genetic models, such as gene knockout (KO) mouse models, have been valuable in studying Eomes.

In immune cell development, Eomes expression identifies the early bone marrow precursor to classical NK cells. Transfer of EomeshiNKneg cells into Rag2-/-Il2rg-/- recipients generated functional NK cells, while transfer of other ILC precursors did not, demonstrating that the NK and ILC1 lineages diverge early during development [1]. In CD4+ T cells, Eomes deletion protected against central nervous system (CNS) inflammation. Eomes is required for long-term maintenance of CNS-infiltrating CD4+ T cells, associated with sustained expression of genes involved in mitochondrial organization and functions [2]. In human NK cells, deleting T-BET and Eomes using Nuclease technology compromised in vivo antitumor response, normal proliferation, persistence, and cytokine responses. Eomes-deleted CD56bright NK cells acquired an innate lymphoid cell precursor-like profile [3]. In CD8+ T cells within the tumor microenvironment, Eomes-dependent loss of the co-activating receptor CD226 restrained anti-tumor functions and limited the efficacy of cancer immunotherapy [5].

In conclusion, Eomes is essential for the development and function of multiple immune cell types, with its dysregulation associated with various diseases, especially those related to immune-mediated inflammation and cancer. KO mouse models have been instrumental in revealing these functions, highlighting the significance of Eomes in understanding immune-related disease mechanisms and potentially guiding the development of new immunotherapeutic strategies.

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. 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/

3. 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/

4. Geginat, Jens, Vasco, Chiara, Gruarin, Paola, Pagani, Massimiliano, Abrignani, Sergio. 2023. Eomesodermin-expressing type 1 regulatory (EOMES+ Tr1)-like T cells: Basic biology and role in immune-mediated diseases. In European journal of immunology, 53, e2149775. doi:10.1002/eji.202149775. https://pubmed.ncbi.nlm.nih.gov/36653901/

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/

7. Schüle, Katrin M, Weckerle, Jelena, Probst, Simone, Schlägl, Inga-Marie, Arnold, Sebastian J. 2023. Eomes restricts Brachyury functions at the onset of mouse gastrulation. In Developmental cell, 58, 1627-1642.e7. doi:10.1016/j.devcel.2023.07.023. https://pubmed.ncbi.nlm.nih.gov/37633271/