Regulatory network governing the differentiation of CD4+ T cells. Helikar Tomas thelika@unmc.edu University of Nebraska - Lincoln 2015-06-03T09:30:44Z 2016-01-27T19:10:25Z 2015-11-15T21:16:23Z 2015-11-15T21:16:23Z 2015-11-15T21:16:23Z 2015-11-15T21:16:23Z

Gene Name: GATA3

GATA binding protein 3 [Homo sapiens(human)]

NCBI Gene ID: 2625

UniProt Accession ID: P23771

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Interleukin 10

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Interleukin 4 receptor [Homo sapiens (human)]

UniProt ID: P24394

Gene Name: IL4R

NCBI Gene ID: 3566

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Signal transducer and activator of transcription 4 [Homo sapiens(human)]

UniProt ID: Q14765

Gene Name: STAT4

NCBI Gene ID: 6775

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Signal transducer and activator of transcription 1

Uniport ID: P42224

Gene Name: STAT1

Gene ID: 6772

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Suppressor of cytokine signaling 1

Uniprot ID: O15524

Gene Name: SOCS1

Gene ID: 8651

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interferon gamma receptor 1 [Homo sapiens (human)]

Uniprot ID: P15260

Gene Name: IFNGR1

NCBI Gene ID: 3459

Interferon gamma receptor2 (interferon gamma transducer 1) [Homo sapiens (human)]

Uniprot ID: P38484

Gene Name: IFNGR2

NCBI Gene ID: 3460

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T-box expressed in T cells

T-box 21 (TBX21)

UniProt Accession ID: Q9UL17

Gene Name: TBX21

NCBI Gene ID: 30009

Eomesodermin homolog (Xenopus laevis) (EOMES)

UniProt Accession ID: P79944

Gene Name: tbx21

NCBI Gene ID: 495078

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Signal transducer and activator of transcription 3

Uniprot ID: P40763

Gene: STAT3

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interferon beta receptor [Homo sapiens (human)]

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Interleukin 12 receptor, beta 1 [Homo sapiens(human)]

UniProt ID: P42701

Gene Name: IL12RB1

NCBI Gene ID: 3594

Interleukin 12 receptor, beta 2 [Homo sapiens(human)]

UniProt ID: Q99665

Gene Name: IL12RB2

NCBi Gene ID: 3595

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Interleukin 4 [Homo sapiens (human)]

UniProt ID: P05112

Gene Name: IL4

NCBI Gene ID: 3565

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Signal transducer and activator of transcription 6, interleukin-4 induced [Homo sapiens(human)]

UniProt ID: P42226

Gene Name: STAT6

NCBI Gene ID: 6778

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Interferon, gamma [Homo sapiens(human)]

UniProt Accession ID: P01579

Gene Name: IFNG

NCBI Gene ID: 3458

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Interleukin 18receptor 1 [Homo sapiens (human)]

UniProt ID: Q13478

Gene Name: IL18R1

NCBI Gene Name: 8809

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Interleukin-1 receptor-associated kinase 1 [Homo sapiens (human)]

UniProt ID: P51617

Gene Name: IRAK1

NCBI Gene ID: 3654

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Nuclear factor of activated T-cells, cytoplasmic 1

Uniprot ID: O95644

Gene: NFATC1

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Interleukin 10 receptor

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GATA3 is activated by STAT6 or GATA3. GATA3 is inhibited by T-bet.

In human cells, this interaction is unclear.

Some studies suggest an auto-activatory loop [3-6] in mice.

STAT6 activates GATA3

T-bet inhibits GATA3

S_18 1 S_11 1 S_1 1 S_11 1

GATA3 induces IL10.

IL10 signaling is dependent on GATA3

S_1 1

IL4 receptor is activated by IL4, and inhibited by SOCS1.

SOCS1 inhibits IL4R

IL4 is IL4 receptor ligand

S_16 1 S_7 1

IL12R activates whereas GATA3 inhibits STAT4.

STAT4 mediates IL12R signaling.

GATA can reduce the expression of STAT4

S_14 1 S_1 1

SOCS1 directly inhibits JAK1

S_9 1 S_7 1

STAT1 is activated by IFNgR OR JAK1.

STAT1 can be activated by IFNg or IFNb pathway

S_5 1 S_13 1

STAT1 or Tbet can activate SOCS1

STAT1 induced the activation of SOCS1

T-bet can activate SOCS1 directly or indirectly (via a pathway independent of IFNgR/STAT1)

S_6 1 S_11 1

IFNg receptor is activated by IFNg.

IFNg is IFNg receptor ligand

S_19 1

Tbet is activated by STAT1 or Tbet. GATA3 inhibits Tbet.

T-bet mRNA is inhibited by virus-induced GATA-3 expression. Q: What about under normal conditions?

T-bet induction is STAT1-dependent

T-bet can auto-activate.

S_6 1 S_1 1 S_11 1 S_1 1

Stat3 is activated by IL10R

IL10R directly binds to Stat3

S_23 1

IFNbR is activated upon ligand binding (INFb)

INFb is a ligand for INFb receptor

S_15 1

IL12 receptor is activated by IL12.

IL12 is IL12R ligand.

S_8 1

IL4 is activated by GATA3, and inihibited by STAT1.

IL4 can be induced by GATA3

STAT1 (via IRF1/2) inhibits IL4

S_1 1 S_6 1

IL4R is activated by STAT6

STAT6 is activated by IL4R

S_3 1

IFNg is activated by Tbet, STAT4, OR IRAK.

IRAK activates IFNg. Q: Any experimental evidence?

STAT4 might directly activate IFNg.

T-bet transactivates the IFNg gene and results in increased production of IFNg

S_11 1 S_12 1 S_4 1 S_12 1 S_22 1 S_12 1 S_21 1 S_12 1

IL18R is activated by IL18, and inhibited by STAT6

IL18 activates IL18 receptor.

IL4 can inhibit IL18R via STAT6

S_10 1 S_18 1

IRAK is activated by IL18R

IL18 receptor activates IRAK

S_20 1

NFAT is activated by TCR

TCR binds to, and activates NFAT

S_17 1

IL receptor is activated by its ligand, IL10

IL10 binds and activates its receptor, IL10R

S_2 1