Loss of Canonical Notch Signaling Affects Multiple Steps in NK Cell Development in Mice
| Autor: | Sten Eirik W. Jacobsen, Lilian Wittmann, Hanane Boukarabila, Claudia Peitzsch, Alya Zriwil, P. Chaves, Ewa Sitnicka |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Cytotoxicity
Immunologic 0301 basic medicine endocrine system Cellular differentiation T cell Immunology Cell Notch signaling pathway Biology Lymphocyte Activation Mice 03 medical and health sciences medicine Animals Immunology and Allergy Cytotoxic T cell Lymphopoiesis Progenitor cell Cells Cultured Mice Knockout Receptors Notch Chimera Cell growth Cell Differentiation Lymphoid Progenitor Cells Cell biology Killer Cells Natural Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Immunoglobulin J Recombination Signal Sequence-Binding Protein Signal Transduction |
| Zdroj: | The Journal of Immunology. 201:3307-3319 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Within the hematopoietic system, the Notch pathway is critical for promoting thymic T cell development and suppressing the B and myeloid lineage fates; however, its impact on NK lymphopoiesis is less understood. To study the role of Notch during NK cell development in vivo, we investigated different NK cell compartments and function in Rbp-Jkfl/flVav-Cretg/+ mice, in which Rbp-Jk, the major transcriptional effector of canonical Notch signaling, was specifically deleted in all hematopoietic cells. Peripheral conventional cytotoxic NK cells in Rbp-Jk–deleted mice were significantly reduced and had an activated phenotype. Furthermore, the pool of early NK cell progenitors in the bone marrow was decreased, whereas immature NK cells were increased, leading to a block in NK cell maturation. These changes were cell intrinsic as the hematopoietic chimeras generated after transplantation of Rbp-Jk–deficient bone marrow cells had the same NK cell phenotype as the Rbp-Jk–deleted donor mice, whereas the wild-type competitors did not. The expression of several crucial NK cell regulatory pathways was significantly altered after Rbp-Jk deletion. Together, these results demonstrate the involvement of canonical Notch signaling in regulation of multiple stages of NK cell development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|