| First Author | Peterson TV | Year | 2019 |
| Journal | Front Immunol | Volume | 10 |
| Pages | 1911 | PubMed ID | 31456807 |
| Mgi Jnum | J:355197 | Mgi Id | MGI:7737845 |
| Doi | 10.3389/fimmu.2019.01911 | Citation | Peterson TV, et al. (2019) Conditional Deletion of the V-ATPase a2-Subunit Disrupts Intrathymic T Cell Development. Front Immunol 10:1911 |
| abstractText | Proper orchestration of T lymphocyte development is critical, as T cells underlie nearly all responses of the adaptive immune system. Developing thymocytes differentiate in response to environmental cues carried from cell surface receptors to the nucleus, shaping a distinct transcriptional program that defines their developmental outcome. Our recent work has identified a previously undescribed role for the vacuolar ATPase (V-ATPase) in facilitating the development of murine thymocytes progressing toward the CD4(+) and CD8(+) alphabeta T cell lineages. Vav1(Cre) recombinase-mediated deletion of the a2 isoform of the V-ATPase (a2V) in mouse hematopoietic cells leads to a specific and profound loss of peripheral CD4(+) and CD8(+) alphabeta T cells. Utilizing T cell-restricted Lck(Cre) and CD4(Cre) strains, we further traced this deficiency to the thymus and found that a2V plays a cell-intrinsic role throughout intrathymic development. Loss of a2V manifests as a partial obstruction in the double negative stage of T cell development, and later, a near complete failure of positive selection. These data deepen our understanding of the biological mechanisms that orchestrate T cell development and lend credence to the recent focus on V-ATPase as a potential chemotherapeutic target to combat proliferative potential in T cell lymphoblastic leukemias and autoimmune disease. |
