Differential induction of Id3 signals lineage divergence, Notch-independent differentiation, and functional maturation of γδ T cells
| Autor: | Lauritsen, Jens Peter Holst, Wong, Gladys W., Lee, Sang-Yun, Lefebvre, Juliette M., Ciofani, Maria, Rhodes, Michele, Kappes, Dietmar J., Zúñiga-Pflücker, Juan Carlos, Wiest, David L. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Mice
Knockout Receptors Notch Cell Differentiation Mice Transgenic Receptors Antigen T-Cell gamma-delta Thymus Gland Article Mice T-Lymphocyte Subsets Animals Cell Lineage Inhibitor of Differentiation Proteins Extracellular Signal-Regulated MAP Kinases RGS Proteins Early Growth Response Protein 1 Signal Transduction |
| Popis: | alphabeta and gammadelta T cells arise from a common thymocyte progenitor during development in the thymus. Emerging evidence suggests that the pre-T cell receptor (pre-TCR) and gammadelta T cell receptor (gammadeltaTCR) play instructional roles in specifying the alphabeta and gammadelta T-lineage fates, respectively. Nevertheless, the signaling pathways differentially engaged to specify fate and promote the development of these lineages remain poorly understood. Here, we show that differential activation of the extracellular signal-related kinase (ERK)-early growth response gene (Egr)-inhibitor of DNA binding 3 (Id3) pathway plays a defining role in this process. In particular, Id3 expression served to regulate adoption of the gammadelta fate. Moreover, Id3 was both necessary and sufficient to enable gammadelta-lineage cells to differentiate independently of Notch signaling and become competent IFNgamma-producing effectors. Taken together, these findings identify Id3 as a central player that controls both adoption of the gammadelta fate and its maturation in the thymus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|