| First Author | Tsiomita S | Year | 2022 |
| Journal | J Leukoc Biol | Volume | 112 |
| Issue | 4 | Pages | 641-657 |
| PubMed ID | 35258130 | Mgi Jnum | J:345015 |
| Mgi Id | MGI:7356537 | Doi | 10.1002/JLB.1A0720-439R |
| Citation | Tsiomita S, et al. (2022) ETS2 repressor factor (ERF) is involved in T lymphocyte maturation acting as regulator of thymocyte lineage commitment. J Leukoc Biol 112(4):641-657 |
| abstractText | Thymocyte differentiation and lineage commitment is regulated by an extensive network of transcription factors and signaling molecules among which Erk plays a central role. However, Erk effectors as well as the molecular mechanisms underlying this network are not well understood. Erf is a ubiquitously expressed transcriptional repressor regulated by Erk-dependent phosphorylation. Here, we investigated the role of Erf in T cell maturation and lineage commitment, using a double-fluorescent Erf-floxed mouse to produce thymus-specific Erf knockouts. We observed significant accumulation of thymocytes in the CD4/CD8 DP stage, followed by a significant reduction in CD4SP cells, a trend for lower CD8SP cell frequency, and an elevated percentage of gammadelta expressing thymocytes in Erf-deficient mice. Also, an elevated number of CD69(+) TCRbeta(+) cells indicates that thymocytes undergoing positive selection accumulate at this stage. The expression of transcription factors Gata3, ThPOK, and Socs1 that promote CD4(+) cell commitment was significantly decreased in Erf-deficient mice. These findings suggest that Erf is involved in T cell maturation, acting as a positive regulator during CD4 and eventually CD8 lineage commitment, while negatively regulates the production of gammadelta T cells. In addition, Erf-deficient mice displayed decreased percentages of CD4(+) and CD8(+) splenocytes and elevated levels of IL-4 indicating that Erf may have an additional role in the homeostasis, differentiation, and immunologic response of helper and cytotoxic T cells in the periphery. Overall, our results show, for the first time, Erf's involvement in T cell biology suggesting that Erf acts as a potential regulator during thymocyte maturation and thymocyte lineage commitment, in gammadelta T cell generation, as well as in Th cell differentiation. |
