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Full-Text Articles in Medicine and Health Sciences
The Role Of Notch Receptors And Ligands In Regulation Of Immune Responses, Gerard F. Hoyne
The Role Of Notch Receptors And Ligands In Regulation Of Immune Responses, Gerard F. Hoyne
Health Sciences Papers and Journal Articles
Notch signalling has an important role in the immune system in directing cell fate decisions in a range of diverse cell types. We are beginning to obtain a better understanding of the roles that the different Notch ligands and receptors play in both cellular differentiation of precursor cells and the regulation of immune responses by mature lymphocytes in the periphery. This review will examine the key findings that have emerged in relation to function of Notch in differentiation of T cells, B cells and dendritic cells and how modulation of Notch signalling seems to have potential for therapeutic applications in …
Cooperation Between Somatic Ikaros And Notch1 Mutations At The Inception Of T-All, Yovina Sontani, Gavin Chapman, Peter Papathanasiou, Sally Dunwoodie, Christopher C. Goodnow, Gerard F. Hoyne
Cooperation Between Somatic Ikaros And Notch1 Mutations At The Inception Of T-All, Yovina Sontani, Gavin Chapman, Peter Papathanasiou, Sally Dunwoodie, Christopher C. Goodnow, Gerard F. Hoyne
Health Sciences Papers and Journal Articles
To understand the interactions between Notch1 and Ikaros in the evolution of T cell acute lymphoblastic leukemia (T-ALL), we traced the evolution of T-ALL in mice with an inherited Ikaros mutation, Ikzf1Plstc which inactivates DNA binding. DNA-binding Ikaros repressed Notch1 response in transfected cell lines and in CD4+8+ (DP) thymocytes from young pre-leukemic Ikzf1Plstc heterozygous mice. In DP thymocytes, a 50-1000 fold escalation in mRNA for Notch1 target genes Hes1 and Dtx1 preceded thymic lymphoma or leukemia and was closely correlated with the first detectable differentiation abnormalities loss of heterozygosity (LOH) eliminating wild-type Ikzf1, and multiple missense …
A Cell Autonomous Role For The Notch Ligand Delta-Like 3 In Αβ T- Cell Development, Gerard F. Hoyne, Gavin Chapman, Yovina Sontani, Sharon E. Pursglove, Sally L. Dunwoodie
A Cell Autonomous Role For The Notch Ligand Delta-Like 3 In Αβ T- Cell Development, Gerard F. Hoyne, Gavin Chapman, Yovina Sontani, Sharon E. Pursglove, Sally L. Dunwoodie
Health Sciences Papers and Journal Articles
Notch signalling is critical to help direct T-cell lineage commitment in early T-cell progenitors and in the development of αβ T-cells. Epithelial and stromal cell populations in the thymus express the Notch DSL (Delta, Serrate and Lag2) ligands Delta-like 1 (Dll1), Delta-like 4 (Dll4), Jagged 1 and Jagged 2, and induce Notch signalling in thymocytes that express the Notch receptor. At present there is nothing known about the role of the Delta-like 3 (Dll3) ligand in the immune system. Here we describe a novel cell autonomous role for Dll3 in αβ T-cell development. We show that Dll3 cannot activate Notch …