| Cytokine and Subunits | Principal Cell Source | Cytokine Receptor and Subunits ∗ | Principal Cellular Targets and Biologic Effects |
|---|---|---|---|
| Type I Cytokine Family Members | |||
| Interleukin-2 (IL-2) | T cells | CD25 (IL-2Rα) CD122 (IL-2Rβ) CD132 (γc) | T cells: proliferation and differentiation into effector and memory cells; promotes regulatory T cell development, survival, and function NK cells: proliferation, activation |
| Interleukin-3 (IL-3) | T cells | CD123 (IL-3Rα) CD131 (βc) | Immature hematopoietic progenitors: maturation of all hematopoietic lineages |
| Interleukin-4 (IL-4) | CD4 + T cells (Th2, Tfh), mast cells | CD124 (IL-4Rα) CD132 (γc) | B cells: isotype switching to IgE, IgG4 (in humans; IgG1 in mice) T cells: Th2 differentiation, proliferation Macrophages: alternative activation and inhibition of IFN-γ–mediated classical activation |
| Interleukin-5 (IL-5) | CD4 + T cells (Th2), group 2 ILCs | CD125 (IL-5Rα) CD131 (βc) | Eosinophils: activation, increased generation |
| Interleukin-6 (IL-6) | Macrophages, endothelial cells, T cells | CD126 (IL-6Rα) CD130 (gp130) | Liver: synthesis of acute phase protein B cells: proliferation of antibody-producing cells T cells: Th17 differentiation |
| Interleukin-7 (IL-7) | Fibroblasts, bone marrow stromal cells | CD127 (IL-7R) CD132 (γc) | Immature lymphoid progenitors: proliferation of early T and B cell progenitors T lymphocytes: survival of naive and memory cells |
| Interleukin-9 (IL-9) | CD4 + T cells | CD129 (IL-9R) CD132 (γc) | Mast cells, B cells, T cells, and epithelial cells: survival and activation |
| Interleukin-11 (IL-11) | Bone marrow stromal cells | IL-11Rα CD130 (gp130) | Production of platelets |
| Interleukin-12 (IL-12): IL-12A (p35) IL-12B (p40) | Macrophages, dendritic cells | CD212 (IL-12Rβ1) IL-12Rβ2 | T cells: Th1 differentiation NK cells and T cells: IFN-γ synthesis, increased cytotoxic activity |
| Interleukin-13 (IL-13) | CD4 + T cells (Th2), NKT cells, group 2 ILCs, mast cells | CD213a1 (IL-13Rα1) CD213a2 (IL-13Rα2) CD132 (γc) | B cells: isotype switching to IgE Epithelial cells: increased mucus production Macrophages: alternative activation |
| Interleukin-15 (IL-15) | Macrophages, other cell types | IL-15Rα CD122 (IL-2Rβ) CD132 (γc) | NK cells: proliferation T cells: survival and proliferation of memory CD8 + cells |
| Interleukin-17A (IL-17A) Interleukin-17F (IL-17F) | CD4 + T cells (Th17), group 3 ILCs | CD217 (IL-17RA) IL-17RC | Epithelial cells, macrophages and other cell types: increased chemokine and cytokine production; GM-CSF and G-CSF production |
| Interleukin-21 (IL-21) | Tfh cells | CD360 (IL-21R) CD132 (γc) | B cells: activation, proliferation, differentiation |
| Interleukin-23 (IL-23): IL-23A (p19) IL-12B (p40) | Macrophages, dendritic cells | IL-23R CD212 (IL-12Rβ1) | T cells: differentiation and proliferation of Th17 cells |
| Interleukin-25 (IL-25; IL-17E) | T cells, mast cells, eosinophils, macrophages, mucosal epithelial cells | IL-17RB | T cells and various other cell types: expression of IL-4, IL-5, IL-13 |
| Interleukin-27 (IL-27): IL-27 (p28), EBI-3 | Macrophages, dendritic cells | IL-27Rα CD130 (gp130) | T cells: enhancement of Th1 differentiation; inhibition of Th17 differentiation NK cells: IFN-γ synthesis? |
| Interleukin 35 (IL-35) | Treg | IL-12Rβ2 CD130 (gp130) | T cells: inhibits proliferation |
| Stem cell factor (c-Kit ligand) | Bone marrow stromal cells | CD117 (KIT) | Pluripotent hematopoietic stem cells: maturation of all hematopoietic lineages |
| Granulocyte-monocyte CSF (GM-CSF) | T cells, macrophages, endothelial cells, fibroblasts | CD116 (GM-CSFRα) CD131 (βc) | Immature and committed progenitors, mature macrophages: maturation of granulocytes and monocytes, macrophage activation |
| Monocyte CSF (M-CSF, CSF1) | Macrophages, endothelial cells, bone marrow cells, fibroblasts | CD115 (CSF1R) | Committed hematopoietic progenitors: maturation of monocytes |
| Granulocyte CSF (G-CSF, CSF3) | Macrophages, fibroblasts, endothelial cells | CD114 (CSF3R) | Committed hematopoietic progenitors: maturation of granulocytes |
| Thymic stromal lymphopoietin (TSLP) | Keratinocytes, bronchial epithelial cells, fibroblasts, smooth muscle cells, endothelial cells, mast cells, macrophages, granulocytes and dendritic cells | TSLP-receptor CD127 (IL-7R) | Dendritic cells: activation Eosinophils: activation Mast cells: cytokine production T cells: Th2 differentiation |
| Type II Cytokine Family Members | |||
| Interferon-α (IFN-α) (multiple proteins) | Plasmacytoid dendritic cells, macrophages | IFNAR1 CD118 (IFNAR2) | All cells: antiviral state, increased class I MHC expression NK cells: activation |
| Interferon-β (IFN-β) | Fibroblasts, plasmacytoid dendritic cells | IFNAR1 CD118 (IFNAR2) | All cells: antiviral state, increased class I MHC expression NK cells: activation |
| Interferon-γ (IFN-γ) | T cells (Th1, CD8 + T cells), NK cells, group 1 ILCs | CD119 (IFNGR1) IFNGR2 | Macrophages: classical activation (increased microbicidal functions) B cells: isotype switching to opsonizing and complement-fixing IgG subclasses (established in mice, not humans) T cells: Th1 differentiation Various cells: increased expression of class I and class II MHC molecules, increased antigen processing and presentation to T cells |
| Interleukin-10 (IL-10) | Macrophages, T cells (mainly regulatory T cells) | CD210 (IL-10Rα) IL-10Rβ | Macrophages, dendritic cells: inhibition of expression of IL-12, costimulators, and class II MHC |
| Interleukin-22 (IL-22) | Th17 cells | IL-22Rα1 or IL-22Rα2 IL-10Rβ2 | Epithelial cells: production of defensins, increased barrier function Hepatocytes: survival |
| Interleukin-26 (IL-26) | T cells, monocytes | IL-20R1IL-10R2 | Not established |
| Interferon-λs (type III interferons) | Dendritic cells | IFNLR1 (IL-28Rα) CD210B (IL-10Rβ2) | Epithelial cells: antiviral state |
| Leukemia inhibitory factor (LIF) | Embryonic trophectoderm, bone marrow stromal cells | CD118 (LIFR) CD130 (gp130) | Stem cells: block in differentiation |
| Oncostatin M | Bone marrow stromal cells | OSMR CD130 (gp130) | Endothelial cells: regulation of hematopoietic cytokine production Cancer cells: inhibition of proliferation |
| TNF Superfamily Cytokines † | |||
| APRIL (CD256, TNFSF13) | T cells, dendritic cells, monocytes, follicular dendritic cells | TACI (TNFRSF13B) or BCMA (TNFRSF17) | B cells: survival, proliferation |
| BAFF (CD257, TNFSF13B) | Dendritic cells, monocytes, follicular dendritic cells, B cells | BAFF-R (TNFRSF13C) or TACI (TNFRSF13B) or BCMA (TNFRSF17) | B cells: survival, proliferation |
| Lymphotoxin-α (LTα, TNFSF1) | T cells, B cells | CD120a (TNFRSF1) or CD120b (TNFRSF2) | Same as TNF |
| Lymphotoxin-αβ (LTαβ) | T cells, NK cells, follicular B cells, lymphoid inducer cells | LTβR | Lymphoid tissue stromal cells and follicular dendritic cells: chemokine expression and lymphoid organogenesis |
| Tumor necrosis factor (TNF, TNFSF1) | Macrophages, NK cells, T cells | CD120a (TNFRSF1) or CD120b (TNFRSF2) | Endothelial cells: activation (inflammation, coagulation) Neutrophils: activation Hypothalamus: fever Muscle, fat: catabolism (cachexia) |
| Osteoprotegerin (OPG, TNFRSF11B) | Osteoblasts | RANKL | Osteoclast precursor cells: inhibits osteoclast differentiation |
| IL-1 Family Cytokines | |||
| Interleukin-1α (IL-1α) | Macrophages, dendritic cells, fibroblasts, endothelial cells, keratinocytes, hepatocytes | CD121a (IL-1R1) IL-1RAP or CD121b (IL-1R2) | Endothelial cells: activation (inflammation, coagulation) Hypothalamus: fever |
| Interleukin-1β (IL-1β) | Macrophages, dendritic cells, fibroblasts, endothelial cells, keratinocytes | CD121a (IL-1R1) IL-1RAP or CD121b (IL-1R2) | Endothelial cells: activation (inflammation, coagulation) Hypothalamus: fever Liver: synthesis of acute-phase proteins T cells: Th17 differentiation |
| Interleukin-1 receptor antagonist (IL-1RA) | Macrophages | CD121a (IL-1R1) IL-1RAP | Various cells: competitive antagonist of IL-1 |
| Interleukin-18 (IL-18) | Monocytes, macrophages, dendritic cells, Kupffer cells, keratinocytes, chondrocytes, synovial fibroblasts, osteoblasts | CD218a (IL-18Rα) CD218b (IL-18Rβ) | NK cells and T cells: IFN-γ synthesis Monocytes: expression of GM-CSF, TNF, IL-1β Neutrophils: activation, cytokine release |
| Interleukin-33 (IL-33) | Endothelial cells, smooth muscle cells, keratinocytes, fibroblasts | ST2 (IL1RL1) IL-1 Receptor Accessory Protein (IL1RAP) | T cells: Th2 development ILCs: activation of group 2 ILCs |
| Other Cytokines | |||
| Transforming growth factor-β (TGF-β) | T cells (mainly Tregs), macrophages, other cell types | TGF-β R1 TGF-β R2 TGF-β R3 | T cells: inhibition of proliferation and effector functions; differentiation of Th17 and Treg B cells: inhibition of proliferation; IgA production Macrophages: inhibition of activation; stimulation of angiogenic factors Fibroblasts: increased collagen synthesis |
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