Journal of Immunology Research

Review Article

Notch Signaling and T-Helper Cells in EAE/MS

Table 1

Notch and Th subsets.


Ligand/pathway	Method	Results	References

Dll	BMDC LPS stimulation	↑Dll4 mRNA	Amsen et al., 2004 [9]
Dll	Dll1 expressing APC/CD4⁺ T cells coculture	↑IFN-g	Amsen et al., 2004 [9]
Dll	CD8⁻ DCs LPS stimulation	↑Dll4 expression	Skokos and Nussenzweig, 2007 [33]
Dll	Dll4-mFc CD4⁺ T cell treatment	↑IFN-g	Skokos and Nussenzweig, 2007 [33]
Dll	DCs TLR2/TLR9 ligation	↑DCs Dll expression, ↑T-bet, ↑IFN-g, and ↓IL-4 by CD4⁺ T cell	Sun et al., 2008 [34]
Dll	CD4⁺ T cell recDll4 treatment	↑RORc activation, ↑IL-17	Mukherjee et al., 2009 [12]
Dll	CD4⁺ T cell recDll4 treatment	↓phospho-Jak3, ↓phospho-Stat5, and ↓Foxp3	Bassil et al., 2011 [13]
Dll	CD4⁺ CD25⁻ cells Dll4 and Jagged1 pretreatment	↑TGF-βRII and phospho-Smad3	Hue et al., 2012 [15]
Jagged	Jagged1 transduction of human APCs	Induction of IL-10 producing Tr1 cells	Vigouroux et al., 2003 [18]
Jagged	HPCs expressing Jagged2	↑Treg expansion and function	Kared et al., 2006 [19]
Jagged	Notch1 or Jagged1 blockade	↓Treg function	Asano et al., 2008 [20]
Jagged	BMDC LPS stimulation	↑Jagged1 mRNA	Amsen et al., 2004 [9]
Jagged	Jagged1 expressing APCs/CD4⁺ T cells coculture	↑IL-4, ↑IL-5
NICD	NICD forced expression in CD4⁺ T cells	NICD regulates IL4 transcription
NICD	RBP-Jκ/NICD1/Smad3 forced expression in CD4⁺ T cells	RBP-Jκ/NICD1/Smad3 complex binds and transactivates Il9 promoter	Elyaman et al., 2012 [21]
NICD	Cell line transduction	RBP-Jκ binds Tbx21 promoter	Minter et al., 2005 [10]
NICD	Splenocytes aCD3/aCD28 stimulation	NICD binds Ifng promoter	Shin et al., 2006 [11]
NICD	NICD forced expression in CD4⁺ T cells	NICD binds the Gata3 promoter	Fang et al., 2007 [17]
NICD	Notch1 blockade in Th17 cells	↓Th17 associated cytokines	Keerthivasan et al., 2011 [31]
NICD	Cell line transfection	RBP-Jκ binds the Gata3 promoter	Amsen et al., 2007 [16]
Noncanonical	In vivo notch ablation in CD4⁺ cells	Notch1 and Notch2 redundantly essential for Th1 development	Auderset et al., 2012 [23]
Noncanonical	Mutant NICD in Notch1 KO Tregs	NICD targeting plasma membrane improves Treg survival	Perumalsamy et al., 2012 [22]