Reciprocal Control of G1-Phase Progression Is Required for Th-POK/Runx3–Mediated CD4/8 Thymocyte Cell Fate Decision
| Autor: | Chiharu Sato, Yumi Iida, Shin Ichiro Ohno, Katsuto Hozumi, Tatsuya Sugoh, Yoshinori Okada, Masanobu Satake, Hideyuki Saya, Kazuyoshi Kohu, Yasutoshi Agata, Marin Chiba, Akira Akatsuka, Tomoki Chiba, Sonoko Habu, Keiko Miyashita, Hisako Akatsuka, Hideyuki Tanabe, Takehito Sato |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunology Cell Mice Transgenic CD8-Positive T-Lymphocytes Biology Cell fate determination Cell cycle phase Mice Organ Culture Techniques Tumor Cells Cultured medicine Animals Immunology and Allergy Cell Lineage Transcription factor Psychological repression Mice Knockout Genetics Mice Inbred BALB C T-cell receptor G1 Phase Cell Differentiation Cell biology Mice Inbred C57BL Thymocyte Core Binding Factor Alpha 3 Subunit medicine.anatomical_structure CD8 Transcription Factors |
| Zdroj: | Journal of Immunology = Journal of Immunology. 189(9):4426-4436 |
| ISSN: | 0022-1767 |
| Popis: | After receiving a TCR-mediated differentiation signal, CD4 and CD8 double-positive thymocytes diverge into CD4 or CD8 single-positive T cells, for which Th-POK and Runx3 have been identified as pivotal transcription factors, respectively. The cross-antagonistic regulation of Th-POK and Runx3 seems to be essential for CD4/8 thymocyte lineage commitment. However, the process for determining which pivotal factor acts dominantly has not been established. To explore the determining process, we used an in vitro culture system in which CD4 or CD8 single-positive cells are selectively induced from CD4/8 double-positive cells. Surprisingly, we found that control of G1 cell cycle phase progression is critical for the determination. In the CD4 pathway, sustained TCR signal, as well as Th-POK, induces G1-phase extension and represses CD8 expression in a G1 extension-dependent manner. In the CD8 pathway, after receiving a transient TCR signal, the IL-7R signal, as well as Runx3, antagonizes TCR signal-mediated G1 extension and CD8 repression. Importantly, forced G1 extension cancels the functions of Runx3 to repress Th-POK and CD4 and to reactivate CD8. In contrast, it is suggested that forced G1 progression inhibits Th-POK function to repress CD8. Collectively, Th-POK and Runx3 are reciprocally involved in the control of G1-phase progression, on which they exert their functions dependently. These findings may provide novel insight into how CD4/CD8 cell lineages are determined by Th-POK and Runx3. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|