Th1 Differentiation Pathway

Click on one of the boxes below to see the processes that promote Th1 differentiation and the transcription factors, secreted molecules, and some of the cell surface markers that distinguish a differentiated Th1 cell from the other T helper cell subtypes.

TLR
TLR
IL-27
IL-27
IL-12
IL-12
MHC II
MHC II
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TCR-CD3
TCR-CD3
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CD4
CD4
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CD28
CD28
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B7
B7
IL-27
IL-27
IL-27 R alpha/
WSX-1
IL-27 R alpha/
WSX-1
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gp130
gp130
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IL-12 R beta 1
IL-12 R beta 1
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Jak1
Jak1
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Jak1
Jak1
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Jak2
Jak2
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Tyk2
Tyk2
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STAT3
STAT3
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STAT1
STAT1
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STAT1 Dimer
STAT1 Dimer
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STAT1 Dimer
STAT1 Dimer
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STAT1 Dimer
STAT1 Dimer
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T-bet
T-bet
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GATA-3
GATA-3
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Pathogen
Pathogen
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Dendritic Cell
Dendritic Cell
Naive CD4+ T Cell
Naive CD4+ T Cell
IL-18
IL-18
IL-18 R alpha
IL-18 R alpha
IL-18 R beta
IL-18 R beta
IL-27 R alpha/
WSX-1
IL-27 R alpha/
WSX-1
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gp130
gp130
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IL-12
IL-12
IL-12 R beta 1
IL-12 R beta 1
IL-12 R beta 2
IL-12 R beta 2
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Tyk2
Tyk2
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Jak2
Jak2
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Jak2
Jak2
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IFN-gamma
IFN-gamma
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IFN-gamma R1
IFN-gamma R1
IFN-gamma R2
IFN-gamma R2
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Jak1
Jak1
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Jak1
Jak1
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Jak2
Jak2
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STAT4
STAT4
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STAT3
STAT3
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STAT5
STAT5
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STAT1
STAT1
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STAT4 Dimer
STAT4 Dimer
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STAT1 Dimer
STAT1 Dimer
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AP-1
AP-1
IFN-gamma
IFN-gamma
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STAT4 Dimer
STAT4 Dimer
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IFN-gamma
IFN-gamma
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IL-18 R beta
IL-18 R beta
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STAT1 Dimer
STAT1 Dimer
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T-bet
T-bet
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T-bet
T-bet
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IFN-gamma
IFN-gamma
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IL-10
IL-10
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TNF-alpha
TNF-alpha
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TNF-beta
TNF-beta
IFN-gamma
IFN-gamma
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IL-2
IL-2
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Th1 Cell
Th1 Cell
IL-27
IL-27
IL-12
IL-12
IL-27 R alpha/
WSX-1
IL-27 R alpha/
WSX-1
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gp130
gp130
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IL-12 R beta 1
IL-12 R beta 1
IL-12 R beta 2
IL-12 R beta 2
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Jak1
Jak1
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Jak1
Jak1
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Jak2
Jak2
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Tyk2
Tyk2
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STAT3
STAT3
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STAT1
STAT1
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STAT1 Dimer
STAT1 Dimer
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STAT1 Dimer
STAT1 Dimer
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T-bet
T-bet
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T-bet
T-bet
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IFN-gamma
IFN-gamma
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IL-12 R beta 2
IL-12 R beta 2
IFN-gamma
IFN-gamma
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IFN-gamma R1
IFN-gamma R1
IFN-gamma R2
IFN-gamma R2
IFN-gamma
IFN-gamma
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Th1 Cell
Th1 Cell

Overview of Th1 Differentiation

CD4+ T cells play a central role in the adaptive immune response. Following T cell receptor activation and co-stimulation by antigen-presenting cells, naïve CD4+ T cells differentiate into one of several lineages of T helper cell subtypes depending primarily on cytokines present in the extracellular environment. In the presence of IL-27 and IL-12, naïve CD4+ T cells differentiate into T helper type 1 (Th1) cells. Th1 cells are required for host defense against intracellular viral and bacterial pathogens. IL-27 promotes early commitment to the Th1 lineage by activating STAT1 signaling to induce expression of the Th1-specific transcription factor, T-bet, and inhibit expression of the Th2-specific transcription factor, GATA-3. T-bet serves as the master regulator of Th1 differentiation. It promotes expression of both IL-12 R beta 2 and IFN-gamma, the signature cytokine produced by Th1 cells. IL-12 R beta 2 dimerizes with IL-12 R beta 1 to form a functional IL-12 receptor complex. This renders the cells responsive to IL-12, which is critical for Th1 differentiation. IL-12 signaling stimulates STAT4-dependent expression of IFN-gamma and IL-18 R beta. Formation of the IL-18 receptor complex allows IL-18 signaling to further drive IFN-gamma expression through AP-1-dependent transcription. In addition to activation of STAT4, IL-12, along with IFN-gamma, activates STAT1 to maintain T-bet expression and Th1-specific cytokine production.

To learn more, please visit our Th1 Cells Research Area.

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