Cell type

Suggested immunosuppressive mechanisms

Ref

tTreg/nTreg

Require CD28 co-stimulation for their development in thymus

[58] [59] [60]

Il-2 is important for thymic induction of tTreg

[61] [62]

STAT5 has been demonstrated to increase the in vivo frequency of tTreg

[63]

IL-15 is essential for induction of Foxp3 expression in thymocytes

[64]

c-Rel has been shown to be highly expressed by tTreg

[65] [66]

mTECs are responsible for inducing selection of thymic tTreg

[2] [69]

pTreg

TGF-β and its receptor signal pathway is essential for the generation of pTreg

[82] [83] [84]

CNS-1, a non-coding region of Foxp3 locus are a crucial regulatory element in the generation of pTreg

[87] [88]

IL-2 play a vital part in the differentiation of Foxp3⁺ pTreg

[89] [90] [91]

Downstream STAT5-dependent signaling is essential for the differentiation of pTreg

[92] [93] [94]

RA plays a significant role in enhancing the generation of Foxp3 Treg cells in the GALT

[95] [96] [97]

Smad 2 and Smad 3 participate in the pTreg differentiation process

[99] [100]

Tr1

IL-10 is the major cytokine involved in Tr1 cells differentiation pathway

[102]

An essential growth factor for the development of Tr1 is IL-15

[103] [104]

IL-27 are the major cytokines involved in the differentiation of Tr1 cells

[105] [106]

c-Maf which activates IL21 facilitates proliferation of Tr1

[105] [107]

IL21, an autocrine growth factor drives the proliferation of Tr1 cells

[107]

ICOS stimulates the IL27-induced differentiation of Tr1

[105]

AhR induced by IL27 shown to be involved in the differentiation of Tr1

[108] [109]

Th3

Th3 mediate their suppressive activity by the production of TGF-β.

[110]

Th3 exhibit a mutual relationship with Th17 cells and exert regulatory potentials

[111] [112] .

Tr35

Tr35 are involved in IL-35 production

[113]