CD4+FOXP3+ Tregs
Defective FOXP3+ Treg function: a key immunophenotype in type 1 diabetes
Treg immunophenotype observed | Study authors (date) | Individuals studied | Study outcomes |
---|---|---|---|
Reduced Treg IL-2 sensitivity | Long et al (2011) [32] | NDB, stratified by PTPN22 genotype | The T1D-associated genotype was associated with reduced IL-2 signalling |
Garg et al (2012) [34] | NDB stratified by IL2RA genotype | The T1D-associated genotype was associated with reduced IL-2 signalling | |
Yang et al (2015) [39] | With long-standing T1D | Reduced IL-2 signalling was associated with the T1D-associated PTPN2 genotype and lower levels of Treg-mediated suppression | |
Cerosaletti et al (2013) [95] | With T1D; NDB but at risk | Reduced IL-2 signalling was observed in T1D vs NDB; IL-2 signalling was reduced in NDB with T1D-associated PTPN2 and IL2RA genotypes | |
Long et al (2010) [33] | With T1D; NDB | Reduced IL-2 signalling was observed in T1D vs NDB | |
Unstable FOXP3 expression | Long et al (2010) [33] | With T1D; NDB | Reduced FOXP3 expression under conditions of limiting IL-2 in individuals with T1D vs NDB |
Garg et al (2012) [34] | NDB stratified by IL2RA genotype | The T1D-associated genotype was associated with reduced FOXP3 expression under conditions of limiting IL-2 | |
Increased Treg apoptosis | Glisic-Milosavljevic et al (2007) [26] | With recent-onset and long-standing T1D; islet AAb+ (at-risk); NDB | Increased Treg apoptosis was observed in recent-onset T1D and at-risk individuals with two or three AAbs when compared to low risk individuals and NDB |
Glisic-Milosavljevic et al (2007) [25] | With new-onset T1D; NDB | Longitudinal study showing increased levels of Treg apoptosis close to diagnosis of T1D vs NDB, but this diminished over time | |
With recent-onset T1D; with long-standing T1D; NDB | Increased levels of Treg apoptosis was observed in recent-onset T1D vs NDB and associated with the high-risk HLA-DQB1 haplotype | ||
Increased Treg proinflammatory cytokine secretion | McClymont et al (2011) [35] | With established T1D; NDB | Increased frequency of IFN-γ-producing Tregs in individuals with T1D vs NDB; these Tregs displayed reduced suppressive function compared with non-IFN-γ-producing Tregs |
Marwaha et al (2010) [36] | With recent-onset T1D; NDB | Increased frequency of IL-17-producing cells in CD45RA−CD25intFOXP3low T cells vs NDB, which displayed reduced suppressive function | |
Altered Treg transcriptome | Pesenacker et al (2016) [37] | With recent-onset T1D; with established T1D; NDB | Identified a panel of genes that are differentially expressed in Tregs from children with recent-onset T1D vs NDB |
Ferraro et al (2014) [38] | With established T1D, with T2D; NDB | A number of genes were shown to have reduced expression in individuals with T1D vs those without |