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Cytokine Function

Cytokine function / Function of cytokine

Cytokines are a large group of proteins, peptides or glycoproteins that are secreted by specific cells of immune system. Cytokines are a category of signaling molecules that mediate and regulate immunity, inflammation and hematopoiesis. Cytokines are produced throughout the body by cells of diverse embryological origin. Cytokine is a general name; other names are defined based on their presumed function, cell of secretion, or target of action. For example, cytokines made by lymphocytes can also be referred to as lymphokines, while interleukins are made by one leukocyte and act on other leukocytes. And chemokines are cytokines with chemotactic activities. Cytokines may act on the cells that secrete them (autocrine action), on nearby cells (paracrine action), or in some instances on distant cells (endocrine action).

Cytokines generally function as intercellular messenger molecules that evoke particular biological activities after binding to a receptor on a responsive target cell.

Cytokine function table

Interleukin

Cytokine Cytokine
Receptor
Cytokine
Source
Cytokine
Targets
Cytokine
Main Function
Cytokine
Disease Association
IL-1α; IL-1b IL1RI and IL1R-AcP Macrophages, many others Macrophages, thymocytes, CNS, others Inflammatory; promotes activation, costimulation, and secretion of cytokines and other acute-phase proteins; pyrogenic ↑ = inflammatory bone resorption; gout; promotes Th17 response
IL-1ra (antagonist) Soluble decoyreceptor: IL1RII and IL1R-AcP     IL-1ra and the soluble decoy receptor complex inhibit IL-1-mediated inflammatory responses  
IL-2 IL2Rα, IL2Rb, and IL2Rγ T cells T, B, NK cells, and macrophages Proliferation; enhancement of cytotoxicity, IFNγ secretion, and antibody production ↓ = lymphoproliferative disease and susceptibility to autoimmune disease; reduced Treg development. ↑ = reduced Th17 development.
IL-3 IL3Rα and IL3Rb T cells, mast cells, eosinophils Hematopoietic progenitors, macro- phages, mast cells Differentiation and survival of lymphoid and myeloid compartment  
IL-4 IL4Rα and IL2Rγ or IL4Rα and IL13Ra1, IL13Ra2 T cells, mast cells T cells, B cells, macrophages, monocytes Proliferation; differentiation of Th2; promotes IgG and IgE production; inhibits cell-mediated immunity and Th17 development ↓ = susceptibility to extracellular pathogens and decreased response to allergens. ↑ = allergic asthma.
IL-5 IL5Rα and IL3Rb Th2 cells Eosinophils, B cells Proliferation and activation; hallmark of Th2 effector cells ↓ = eosinophil and B-1 cell deficiency. ↑ = allergic asthma.
IL-6 IL6Rα and gp130 Macrophages, T cells, fibroblasts, and others Wide variety of cells: B cells, T cells, thymocytes, myeloid cells, osteoclasts Inflammatory and costimulatory action; induces proliferation and differentiation; synergizes with TGFb to drive Th17 ↓ = deficient innate immunity and acute- phase responses, lymphopenia
IL-7 IL7Rα and IL2Rγ Thymic stromal cells, bone marrow, and spleen B cells, T cells, thymocytes Homeostasis, differentia- tion, and survival ↓ = severe combined immune deficiency (SCID)
IL-9 IL9R and IL2Rγ T cells (Th2) T cells, mast cells, neutrophils, epithelial cells Proliferation; promotes Th2 cytokine secretion  
IL-10 IL10R1 and IL10R2 Differentiated T helper cells, Tregs, B cells, dendritic cells, others Macrophages, T cells, dendritic cells, B cells Immune suppression; decreases antigen presentation and MHC class II expression of dendritic cells; down- regulates pathogenic Th1, Th2, and Th17 responses ↓ = immune pathology due to uncon- trolled inflammation. ↑ = inhibits sterile immunity to some pathogens.
IL-11 IL11Rα and gp130 Stromal cells Hematopoietic stem cells, B cells, megakaryocytes Proliferation ↑ = exacerbates airway diseases
IL-12 (p35 + p40) IL12Rb1 and IL12Rb2 Macrophages, dendritic cells, B cells, neutrophils T cells, NK cells Differentiation and proliferation; promotes Th1 and cytotoxicity ↓ = impaired Th1 responses and increased susceptibility to intracellular pathogens
IL-13 IL13Ra1, IL13Ra2 and IL4Rα T cells B cells, macro- phages, others Goblet cell activation in lung and gut; proliferation and promotion of IgE production; regulation of cell-mediated immunity ↓ = impaired Th2 responses to extracel- lular pathogens and allergens. ↑ = exacerbates airway diseases.
IL-14 Not defined T cells B cells Promotion of B cell growth  
IL-15 IL15Rα, IL2Rb, and IL2Rγ Broad expression in hematopoietic cells T cells, NK cells, epithelial cells, others Proliferation and survival; cytokine production ↓ = deficiency in NK cells and defective generation of memory T cells
IL-16 Not defined T cells, eosinophils, mast cells CD4+ T cells Recruitment of CD4+ T cells  
IL-17A IL17RA or IL17RC Th17 cells and others Mucosal tissues, epithelial and endothelial cells Proinflammatory; protective immunity in lung; tight junction integrity; promotes mobilization of neutrophils and cytokine production by epithelial cells; promotes angiogenesis ↓ = susceptibility to extracellular pathogens ↑ = exacerbates organ- specific autoimmune inflammation
IL-17B   Intestine and pancreas      
IL- 17C   thymus and spleen      
IL-17D   T cells, smooth muscle cells, epithelial cells      
IL-17F IL17RA or IL17RC Th17 cells Mucosal tissues, epithelial and endothelial cells Similar function as IL-17A but with 2 logs lower receptor affinity Not well defined. ↑ = increases neutrophil recruit- ment at high concentration.
IL-18 IL18R and IL18-R-AcP Macrophages, others Th1 cells, NK cells, B cells Proinflammatory; induction of IFNγ ↓ = impairs Th1 responses
IL-19 IL20R1 and IL20R2 Monocytes, others Keratinocytes, other tissues Proinflammatory ↑ = psoriasis
IL-20 IL20R1 or IL22R1 and IL20R2 Monocytes, others Keratinocytes, other tissues Proinflammatory ↑ = psoriasis
IL-21 IL21R and IL2Rγ Differentiated T helper cells (Th2 and Th17 subsets) T cells, B cells, NK cells, dendritic cells Proliferation of T cells; promotes differentia- tion of B cells and NK cytotoxicity  
IL-22 IL22R1 and IL10R2; IL22BP Th1 and Th17 cells, NK cells Fibroblasts, epithelial cells Inflammatory, antimicrobial ↑ = psoriasis
IL-23 (p19 + p40) IL23R and IL12Rb1 Macrophages and dendritic cells T cells Inflammatory; promotes proliferation of Th17 cells ↓ = susceptibility to extracellular pathogens. ↑ = exacerbates organ- specific autoimmune inflammation.
IL-24 IL20R1, IL22R1, IL20R2 Monocytes, CD4+ T cells Keratinocytes   ↑ = antitumor effects
IL-25 (IL-17E) IL17RB Th2 cells, mast cells Non-B, non-T, cKit+, FcεR− cells Promotes Th2 differentiation and proliferation ↓ = impairs Th2 responses to extracellular pathogens such as worms
IL-26 IL22R1 and IL10R2 Activated T cells      
IL-27 (p28 + EBI3) WSX-1 and gp130 Activated dendritic cells T cells, others Induction of early Th1 differentiation by stimulating expression of the Tbet transcrip- tion factor; Inhibition of effector Th17 cel responses by inducing STAT-1-dependent blockade of IL-17 production ↓ = immune pathology due to uncontrolled inflamma- tory response
IL-28A/B/IL29 (IFNλ family) IL28R1 and IL10R2 Activated subsets of dendritic cells?   May promote antiviral responses  
IL-30 (p28 subunit of IL-27)          
IL-31 IL31Rα and OSM-Rβ Activated T cells Myeloid progenitors, lung epithelial cells, keratinocytes Proinflammatory ↑ = atopic dermatitis; allergic asthma
IL-32       Induces proinflammatory cytokine production  
IL-33 ST2 and IL1R-AcP Macrophages, dendritic cells Mast cells, Th2 cells Costimulation, promotes Th2 cytokine production ↑ = atopic dermatitis, allergic asthma
IL-35 (p35 + EBI3)   Tregs Effector T cells Immune suppression  

Tumor Necrosis Factor (TNF)

Cytokine Cytokine
Receptor
Cytokine
Source
Cytokine
Targets
Cytokine
Main Function
Cytokine
Disease Association
TNF alpha

Murine: TNFR,p55; TNFR,p75

Human: TNFR,p60; TNFR,p80

Macrophages, monocytes, T cells, others Neutrophils, macrophages, monocytes, endothelial cells Inflammatory; promotes activation and production of acute-phase proteins ↓ = disregulated fever; increased susceptibility to bacterial infection; enhanced resistance to LPS-induced septic shock ↑ = exacerbation of arthritis and colitis
LT alpha

Murine: TNFR,p55; TNFR,p75

Human: TNFR,p60; TNFR,p80

T cells, B cells Many cell types Promotes activation and cytotoxicity; development of lymph nodes and Peyer’s patches ↓ = defective response to bacterial pathogens; absence of peripheral lymph nodes and Peyer’s patches
LT beta LTbR T cells, B cells Myeloid cells, other cell types Peripheral lymph node development; proinflammatory ↓ = increased susceptibility to bacterial infection; absence of lymph nodes and Peyer’s patches ↑ = ectopic lymph node formation
LIGHT LTbR, DcR3, HVEM Activated T cells, monocytes, DCs B cells, NK cells, DCs, other tissue Costimulatory; promotes CTL activity ↓ = defective CD8 T cell costimulation
TWEAK Fn14 Monocytes, macrophages, endothelial Tissue progenitors, epithelial, endothelial Proinflammatory; promotes cell growth for tissue repair and remodeling  
APRIL TACI, BAFF-R, BCMA Macrophages, DCs B cell subsets Promotes T cell- independent responses; B cell homeostasis and differentiation ↓ = impaired class switching to IgA
BAFF (BlyS) TACI, BAFF-R, BCMA Macrophages, DCs, astrocytes B cells B cell maturation and survival ↓ = B cell lymphopenia; defective humoral immunity ↑ = SLE-like syndrome
TL1A DcR3, DR3 Macrophages, endothelial cells Activated T cells Promotes proliferation and cytokine production GITRL
GITRL GITR DCs, macrophages, B cells, others T regulatory cells, activated T cells Costimulatory  
OX40L OX40 Activated T cells, B cells, DCs, monocytes T cells, B cells, DCs Costimulatory; activation and migration of monocytes ↓ = impaired humoral responses
CD40L (CD154) CD40 T cells, monocytes, macrophages, others B cells, APCs Costimulatory; promotes T cell- dependent responses; B cell differentiation and class switching ↓ = defective antibody responses and germinal center formation; hyper-IgM syndrome ↑ = SLE-like syndrome
FASL FAS, DcR3 Activated T cells, B cells, and NK cells APCs, many other cell types Regulatory; pro apoptotic ↓ = lymphoproliferative disease and systemic autoimmunity
CD27L (CD70) CD27 Activated T cel s, B cells, DCs, monocytes T cells, activated B cells Costimulatory  
CD30L (CD153) CD30 Neutrophils, B cells, macrophages, activated T cells T cells, B cells Costimulatory; promotes proliferation and cytokine production Viral CD30 blocks Th1 response
4-1BBL 4-1BB Activated T cells, B cells, DCs, mono- cytes, macrophages Activated T cells, B cells, DCs Costimulatory; promotes activation and migration of monocytes  
TRAIL TRAIL-R1 (DR4), R2 (DR5), R3 (DcR1), and R4 (DcR2) Activated NK cells, T cells Many cell types Costimulatory; promotes NK cell functions; proapoptotic ↓ = defective NK-mediated antitumor response ↑ = enhanced responsiveness to autoantigens
RANK Ligand (TRANCE) RANK receptor or osteoprotegrin T cells and osteoblasts Osteoclasts, many cell types Costimulatory; promotes osteoclasto- genesis and cytokine production ↓ = osteopetrosis ↑ = osteoporosis

Other Cytokines

Cytokine Cytokine
Receptor
Cytokine
Source
Cytokine
Targets
Cytokine
Main Function
Cytokine
Disease Association
FLT3 Ligand Receptor tyrosine kinases Diverse tissue DCs, other myeloid cells Differentiation and proliferation; synergizes with stem cell factor ↓ = impaired hematopoietic stem cell repopulation and B cell precursors
G-CSF GCSFR dimer Macrophages, fibroblasts, other tissues Committed progenitors Differentiation and activation of granulocytes ↓ = neutropenia
GM-CSF GM-CSFRα, βc T cells, macrophages, fibroblasts, others Macrophages, granulocytes, dendritic cells, and progenitors Inflammatory; induction of activation; differ- entiation, growth, and survival ↓ = affects alveolar function
IFNα, IFNβ, IFNω IFNαR1, IFNαR2 Macrophages, fibroblasts, plasmacytoid DCs, others NK cells, many others Promotes resistance to viral pathogens; promotes increased expression of MHC class I ↓ = impaired antiviral responses
IFNγ IFNγR1, IFNγR2 Th1 cells, NK cells, CD8 T cells Macrophages, NK cells, T cells, others Promotes activation of APCs and cell-mediated immunity; increased MHC class II expression ↓ = susceptibility to intracellular pathogens
LIF LIFR, gp130 Macrophages, T cells, fibroblasts, uterus, others Embryonic stem cells, hematopoietic cells, others Cell survival ↓ = deficient hematopoietic progenitor cells; defective blastocyst implantation
M-CSF Receptor tyrosine kinases Monocytes, fibroblasts, others Committed myeloid progenitors Differentiation; prolifera- tion and survival ↓ = monocyte deficiency; osteopetrosis
MIF CD74 trimer, CD44 Macrophages, T cells Macrophages Cell migration, DTH response ↓ = susceptibility to Gram-negative bacteria
OSM LIFR or OSM- Rβ, gp130 Macrophages, fibroblasts, others Myeloid cells, embryonic stem cells, T cells, others Differentiation; induction of immune response (early)  
Stem Cell Factor (SCF) Receptor tyrosine kinases Bone marrow Stem cells, mast cells Activation and growth ↓ = impaired hematopoietic stem cell proliferation and melanocyte production
TGFβ1, TGFβ2, TGFβ3 TGFβR type I, type II, and type III T cells, DCs, macrophages, others All leukocyte populations Regulatory; inhibits growth and activation; Treg maintenance; synergizes with IL-6 to promote Th17 ↓ = increased susceptibility to autoimmune disorders ↑ = fibrotic diseases
TSLP Ligand TSLPR, IL7Rα Skin, lung, and gut DCs and other myeloid cells Promotes Th2 develop- ment (human); B cell development (mouse) ↑ = atopic diseases

References

  1. SnapShot: Cytokines I Cristina M. Tato and Daniel J. Cell 132, p. 324
  2. SnapShot: Cytokines II Cristina M. Tato and Daniel J. Cell 132, p. 500
  3. SnapShot: Cytokines III Cristina M. Tato and Daniel J. Cell 132, p. 900
  4. SnapShot: Cytokines IV Cristina M. Tato and Daniel J. Cell 132, p. 1062

Cytokine related information

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