IL-21 Signaling Pathways and their Primary Biological Effects in Different Immune Cell Types

Click on one of the buttons below to see either the IL-21 signaling pathways or information related to one of the other common cytokine receptor gamma-chain family members.

IL-21
IL-21
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IL-21 R
IL-21 R
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CXCR5
CXCR5
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IL-21
IL-21
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IL-21 R
IL-21 R
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CXCR5
CXCR5
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CXCR5
CXCR5
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CXCR5
CXCR5
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Promotes Follicular Helper T Cell Generation
& Germinal Center Formation
Promotes Follicular Helper T Cell Generation
& Germinal Center Formation
B Cell
B Cell
Activated
CD4+ T Cell
Activated
CD4+ T Cell
Developing Germinal Center
Developing Germinal Center
Centrocyte
Centrocyte
Tfh Cell
Tfh Cell
Plasma Cell
Plasma Cell
Memory B Cell
Memory B Cell

Follicular Helper T Cell Differentiation

Follicular Helper T Cell Differentiation

IL-6
IL-6
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IL-6 R
IL-6 R
TGF-beta
TGF-beta
TGF-beta R
TGF-beta R
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STAT3
STAT3
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IL-21
IL-21
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IL-23 R
IL-23 R
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ROR gamma t
ROR gamma t
IL-21
IL-21
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IL-1 beta
IL-1 beta
IL-23
IL-23
IL-21 R
IL-21 R
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STAT3
STAT3
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ROR gamma t
ROR gamma t
IL-17A, F
IL-17A, F
IL-22
IL-22
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Promotes Th17 Differentiation
Promotes Th17 Differentiation
Dendritic Cell
Dendritic Cell
Naive T Cell
Naive T Cell
Differentiating T Cell
Differentiating T Cell
Th17 Cell
Th17 Cell

Th17 Differentiation

Th17 Differentiation

IL-21
IL-21
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IL-21 R
IL-21 R
IFN-gamma
IFN-gamma
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IL-21
IL-21
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IL-21 R
IL-21 R
IFN-gamma
IFN-gamma
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IL-21
IL-21
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IL-21 R
IL-21 R
Granzyme B
Granzyme B
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Enhances Cytotoxicity of CD8+ T Cells,
Natural Killer Cells &
Natural Killer T Cells
Enhances Cytotoxicity of CD8+ T Cells,
Natural Killer Cells &
Natural Killer T Cells
Activated
CD8+ T Cell
Activated
CD8+ T Cell
Proliferation
Proliferation
Perforin Production
Perforin Production
Natural Killer Cell
Natural Killer Cell
Perforin Production
Perforin Production
Granular Morphology
Granular Morphology
Natural Killer T Cell
Natural Killer T Cell
Granular Morphology
Granular Morphology

Increased Cytotoxicity

Increased Cytotoxicity

IL-21
IL-21
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IL-21 R
IL-21 R
IL-4 R
IL-4 R
IL-4
IL-4
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IL-21
IL-21
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IL-21 R
IL-21 R
IL-21 R
IL-21 R
Promotes B Cell Proliferation
& Differentiation
Promotes B Cell Proliferation
& Differentiation
Antigen
Antigen
BCR
BCR
B Cell
B Cell

Proliferation

Proliferation

Differentiation

Differentiation

Plasma Cells
Plasma Cells
Memory B Cells
Memory B Cells

B Cell Effects

B Cell Effects

IL-21
IL-21
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IL-21 R
IL-21 R
TLR
TLR
Promotes B Cell Apoptosis in the
Absence of BCR & T Cell Signals
Promotes B Cell Apoptosis in the
Absence of BCR & T Cell Signals
Immature B Cell
Immature B Cell
TLR Signal
+
No BCR or T Cell
Interaction
Signal
TLR Signal
+
No BCR or T Cell
Interaction
Signal

Cell Death

Cell Death

B Cell Apoptosis

B Cell Apoptosis

IL-21
IL-21
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IL-21 R
IL-21 R
IL-4
IL-4
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IL-4 R
IL-4 R
Regulates Immunoglobulin Production
& Class Switching
Regulates Immunoglobulin Production
& Class Switching
Activated B Cell
Activated B Cell
Plasma Cell
Plasma Cell

IgG1, IgG2A, IgG2B, IgE
Production

IgG1, IgG2A, IgG2B, IgE
Production

IL-21
IL-21
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IL-21 R
IL-21 R
Inhibits Dendritic Cell
Maturation & Function
Inhibits Dendritic Cell
Maturation & Function
Low
Low
MHC II,
MHC II,
Low
Low
CCR7
CCR7
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Expression
Expression
Dendritic Cell
Dendritic Cell

Antigen-presenting Cell Function

Antigen-presenting Cell Function

CD4+ or CD8+ T Cells
CD4+ or CD8+ T Cells

Inhibits T Cell Responses

Inhibits T Cell Responses

Overview of IL-21 Signaling and its Primary Biological Effects in Different Immune Cell Types

Interleukin-21 (IL-21) is the most recently described cytokine belonging to the common cytokine receptor gamma-chain family. Like other common gamma chain family members, IL-21 is a four alpha-helix bundle type I cytokine. It signals through a receptor complex consisting of IL-21 R and common gamma-chain/IL-2 R gamma. IL-21 is produced primarily by CD4+ T cells and natural killer T (NKT) cells and has a broad range of effects on a number of different cell types. IL-21 signaling in CD4+ T cells is required for both Th17 differentiation and the generation of T follicular helper (Tfh) cells, which support B cell differentiation and antibody production in germinal centers. IL-21 also directly regulates B cell proliferation and apoptosis in a context-dependent manner and can promote immunoglobulin production and isotype class switching. In addition, IL-21 signaling enhances the cytotoxicity of CD8+ T cells, natural killer cells, and NKT cells.

To learn more, please visit our Common gamma Chain Receptor Family Research Area.