Future Perspectives: Therapeutic Targeting of Notch Signalling May Become a Strategy in Patients Receiving Stem Cell Transplantation for Hematologic Malignancies

Table 2

Therapeutic targeting of Notch in murine autoimmunity in vivo.

Disease and intervention	Therapeutic effect	References
Experimental autoimmune encephalomyelitis (EAE; model of multiple sclerosis)
γ-secretase inhibitor	Inhibition of disease-associated Th1 responses and improvement of symptoms	[8, 58, 67]
Notch1 neutralizing antibodies	No effect on Th1 and Th17 responses	[8, 58]
Notch3 neutralizing antibodies	Decreased Th1 and Th17 responses, inhibition of the ability of myelin-primed T cells to transfer the disease	[8, 58]
DLL1 neutralizing antibodies	Reduced Th1 responses and EAE symptoms	[8, 68]
Activating DLL1-Fc fusion protein	Increased Th1 responses and EAE symptoms	[8, 68]
Neutralizing JAG1 antibodies	EAE disease progression	[8, 68]
Activating JAG1-Fc fusion protein	Improvement of EAE symptoms	[8, 68]
Experimental hepatitis
γ-secretase inhibitor	Reduced Notch1 signalling and FoxP3 expression, spontaneous hepatic lymphocyte infiltration consistent with autoimmune hepatitis (C57BL/6 mice)	[61]
Murine diabetes
Lck-Notch3-IC transgenic mice	Up regulation of the generation and function of CD4^+CD25^+ Treg. The mice failed to develop streptozotocin-induced autoimmune diabetes. Adoptive transfer of the lck-Notch3-IC transgenic CD4^+ cells to wild-type recipients prevented the progression of the disease.	[62]
Exposure to JAG2-expressing hematopoietic progenitor cells	Activation of Notch3 signalling with increased Treg proliferation and prevention of diabetes in NOD mice.	[63]
Multiorgan autoimmune disease
Loss of functional mutation in the Itch ubiquitin ligase	This ligase is involved in Notch1 degradation; homozygous mice develop an autoimmune-like disease mainly affecting lungs, skin, and lymphoid organs.	[2, 69–71]

Abbreviations: Experimental autoimmune encephalomyelitis (EAE), Delta-like (DLL), Jagged (JAG), Helper T cells (Th).