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