Cytokine refers to a large group of cell-signaling molecules between cells that essentially includes of proteins, peptides, and glycoproteins. They either have short or long chain structures. Cytokines released from one cell affect the actions of other cells by binding to receptors on their surface (as the Figure 1 shows). These receptors just like mailboxes. They receive the cytokine's chemical message, and then the receiving cell performs activities based on that message.
Figure 1. The main types of cell producing cytokines.
Cytokines are primarily released by immune system cells in order to generate an immune response. For instance, when white blood cells come in contact with pathogens they immediately release cytokines, which in turn communicate and activate other white blood cells to attack the foreign invader. Based on different functions of cytokines, they are divided into different type, including chemokines, interferons, interleukins, tumor necrosis factor and colony stimulating factor. They can act alone, work together or work against each other, but ultimately the role of cytokines is to help regulate the immune response. Let's focus on the different types of cytokines and their functions.
Chemokines are a series of secreted proteins with small molecular weight (8-10kDa) whose main role is the recruitment of leukocyte subsets under homeostatic and pathological conditions. Currently, more than 50 chemokines have been discovered. There are usually 4 conserved cysteine (C) in the molecule of chemokine, these cysteine form a special tertiary structure through disulfide bond. According to whether other amino acids are inserted between the first two Cs near the molecular amino acid (N-terminus), they are divided into 4 subcategories: CXC (with 1 amino acid residue inserted, also known as ɑ subset); CC (without other amino acid residues inserted, also known as β subset); CX3C (insert 3 other amino acids, also known as γ subset); C (only one C at the N-terminus, also known as δ subset). Both the origin and function of the four subset are different (as the table 1 shows). Additionally, you can view the article named The Overview of Chemokine to obtain more information about chemokines.
Table 1. The Origin and Function of Four Subsets of Chemokines
Subsets | Member | Origin of cells | Function |
---|---|---|---|
CXC chemokines | CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, ..., CXCL16, CXCL17 | Activated macrophages, endothelial cells, fibroblasts and megakaryocytes | Chemotaxis of neutrophils, mediating inflammation. |
CC chemokines | CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, ..., CCL27, CCL28 | Activated T cells | Chemotaxis and activation of monocytes and T cells |
CX3C chemokines | CX3CL1 | Unknown | Chemotactic lymphocytes and macrophages |
C chemokines | XCL1, XCL2 | Unknown | Chemotactic lymphocytes |
Interferon, also known as IFN, is a kind of cytokines which plays important roles in viral defense, tumor inhibition and disease treatment through cytotoxic T cells, NK cells and DC cells, etc. According to the different receptors of the signals transmitted by different interferons, interferons are generally divided into three main types: type I interferon, type II interferon and type III interferon (as the table 2 shows). Additionally, you can view the article named The Overview of Interferon to obtain more information about interferons.
Table 2. The Origin and Function of three Subsets of Interferons
Subsets | Member | Origin of cells | Function |
---|---|---|---|
Type I interferon | IFN-α1, -α2, -α4, -α5, -α6, -α7, -α8, -α10, -α13, -α14, -α16, -α17 and -α21, β, ε, к, and ω | IFN-α is produced by white blood cells (mainly mononuclear phagocytes); IFN-β is produced by fibroblasts. | Inhibits viral replication; enhances the role of MHC II molecules. |
Type II interferon | IFN-γ | Activated Th1 cells, CD8+ CTL cells and NK cells. | Inhibits viral replication; enhances the role of MHC II molecules; activates macrophages; antagonizes the effect of IL-4; inhibits Th2 proliferation; promotes B cell differentiation and proliferation. |
Type III interferon | IFNλ1, IFNλ2, IFNλ3 and IFNλ4 | Unknown | This type of interferon is a new type of interferon, and there are few related studies. At present, clinical research is limited to the treatment of viral hepatitis. |
Interleukin is a kind of cytokines, which plays a critical role in immunological regulation and homeostasis. The members of interleukin are wealthy which are named IL-1~IL-38. The interleukin receptors can be classified as type I, type II and other type. The type II interleukin receptors include interleukin-10, 20, 22, 28 receptors, the other type include interleukin-1, 8 receptors, the rest of them are type I interleukin receptors. In this section, we collect the receptor, source and function of all of the interleukins on the table 3. Additionally, you can view the article named The Overview of Interleukin to obtain more information about interleukins.
Table 3. The Origin and Function of Interleukins
Cytokine | Receptor | Source | Main Function |
---|---|---|---|
IL-1α; IL-1β | IL1RI and IL1R2 | Monocytes, macrophages, dendritic cells, NK cells, B cells and endothelial cells | Inflammatory; promotes activation, costimulation, secretion of cytokines and other acute-phase proteins and bone resorption. |
IL-2 | IL2RA, IL2RB, and IL2RG | Th1 cells | Proliferation; enhancement of cytotoxicity, IFNγ secretion, and antibody production. |
IL-3 | IL3RA and IL3RB | T cells, mast cells, NK cells | Hematopoietic cell precursor growth and differentiation; mast cell growth. |
IL-4 | IL4R | Th2 cells, Tc2 cells, NK cells, NKT cells, γδT cells, mast cells | Proliferation; promotes IgG and IgE production and Th2 differentiation; inhibits cell-mediated immunity and Th17 development; enhances macrophage endocytosis. |
IL-5 | IL5RA and IL3RB | Th2 cells and mast cells | Induces eosinophilic and activated B cell proliferation; hallmark of Th2 effector cells. |
IL-6 | IL6R | Monocytes, macrophages, Th2 cells, fibroblasts, dendritic cells and bone marrow stromal cells. | Inflammatory and costimulatory action; induces proliferation and differentiation; synergizes with TGFβ to drive Th17; induces protein expression in the acute phase. |
IL-7 | IL7R | Thymic stromal cells, bone marrow | Homeostasis, differentiation, and mature T cells activation. |
IL-9 | IL9R | Th2 cells | Proliferation; promotes Th2 cytokine secretion; enhances hypertrophic growth. |
IL-10 | IL10R1 and IL10R2 | Differentiated T helper cells, Tc cells, B cells, monocytes and macrophages | Immune suppression; decreases antigen presentation and MHC class II expression of dendritic cells; down-regulates pathogenic Th1, Th2, and Th17 responses; Inhibits T cell proliferation; enhances B differentiation. |
IL-11 | IL11RA | Bone marrow stromal cells | Proliferation; induces protein expression in the acute phase. |
IL-12α | IL12Rb1 and IL12Rb2 | Macrophages, monocytes, dendritic cells and B cells | Differentiation and proliferation; promotes Th1 and cytotoxicity. |
IL-13 | IL13Ra1 and IL13Ra2 | Th2 cells and mast cells | Goblet cell activation in lung and gut; proliferation and promotion of IgE production; regulation of cell-mediated immunity; induces endothelial cells VCAM-1 expression. |
IL-14 | Not defined | T cells | Promotion of B cell growth. |
IL-15 | IL15RA | Broad expression in hematopoietic cells | Proliferation and survival; cytokine production; one of the chemokines of T cells; stimulates the growth of small intestinal epithelial cells. |
IL-16 | CD4 | Th cells and Tc cells | Recruitment of CD4+ T cells |
IL-17A | IL17RA or IL17RC | Th17 cells, NK cells and others | Proinflammatory; protective immunity in lung; tight junction integrity; promotes mobilization of neutrophils and cytokine production by epithelial cells; promotes angiogenesis. |
IL-17B | Unknown | Intestine and pancreas | Unknown |
IL-17C | Unknown | thymus and spleen | Unknown |
IL-17D | Unknown | T cells, smooth muscle cells, epithelial cells | Unknown |
IL-17F | IL17RA or IL17RC | Th17 cells, NK cells and others | Similar function as IL-17A but with 2 logs lower receptor affinity. |
IL-18 | IL18R1 | Macrophages and dendritic cells | Proinflammatory; induction of IFNγ. |
IL-19 | IL20R1 and IL20R2 | Monocytes | Regulates Th1 activity. |
IL-20 | IL20R1 and IL20R2 | Monocytes and keratinocytes | Regulates skin inflammation. |
IL-21 | IL21R | Differentiated T helper cells (Th2 and Th17 subsets) | Proliferation of T cells; promotes differentia tion of B cells and NK cytotoxicity. |
IL-22 | IL22RA1 | Th1 and Th17 cells | Inhibits Th2 cell to produce IL-4. |
IL-23 | IL23R and IL12RB1 | Dendritic cells | Inflammatory; promotes proliferation of Th17 cells. |
IL-24 | IL20R1 and IL20R2 | Monocytes, macrophages and Th2 cells | Induces TNF, IL-1, IL-6 expression and induces anti-tumor activity. |
IL-25 | IL17RB | Th1 cells, mast cells and macrophages | Promotes Th2 differentiation and proliferation. |
IL-26 | IL22RA1 and IL10R2 | Activated T cells and NK cells | Enhances the production of IL-8 and IL-10 by epithelial cells. |
IL-27 | IL27RA | Activated dendritic cells and monocytes | Induces Th1 response; enhances IFNγ production. |
IL-28 | IL28R | Dendritic cells and monocytes | May promote antiviral responses. |
IL-29 | Unknown | Dendritic cells and monocytes | May promote antiviral responses. |
IL-30 | Unknown | APC | Synergy with IL-12 induces IFNγ expression. |
IL-31 | IL31Rα | Activated T cells | Proinflammatory. |
IL-32 | Unknown | Nk cells and T cells | Induces proinflammatory cytokine production. |
IL-33 | Unknown | Stromal cells and dendritic cells | Costimulation, promotes Th2 cytokine production; Mediates the chemotaxis of basophils and mast cells. |
IL-35 | Unknown | Tregs | Immune suppression of Th1, Th2 and Th17; stimulates Treg proliferation. |
IL-37 | Unknown | Unknown | Anti-inflammatory effect, may be an antagonist of IL-18R; not expressed in mice. |
IL-38 | Unknown | Unknown | Anti-inflammatory effect, IL-36α isoform, may be an antagonist of IL-36 receptor. |
Tumor necrosis factor, abbreviated TNF or TNFɑ, is one of multiple proteins capable of inducing necrosis (death) of tumor cells that possess a wide range of proinflammatory actions. TNF is a multifunctional cytokine with effects on lipid metabolism, coagulation, insulin resistance, and the function of endothelial cells lining blood vessels. Broadly, TNF superfamily refers to a superfamily of cytokines that can cause cell death. Nineteen proteins have been identified as part of the TNF family on the basis of sequence, function, and structural similarities. Besides EDA1 and EDA2, seventeen members of TNF superfamily are shown in table 3. Additionally, you can view the article named Tumor Necrosis Factor (TNF) to obtain more information about TNF.
Table 4. The Origin and Function of TNF Family
Cytokine | Receptor | Source | Main Function |
---|---|---|---|
TNFα | TNFR1 and TNFR2 | Macrophages, monocytes, Th cells, dendritic cells, mast cells, NK cells, B cells | Inflammatory; promotes activation and production of acute-phase proteins; induces endothelial cell E-selectin production. |
TNF-β (LTα) | TNFR1 and TNFR2 | Th1 cell, Tc cells, B cells | Promotes activation and cytotoxicity; development of lymph nodes and Peyer's patches; enhances endocytosis of neutrophils and macrophages. |
LTβ | LTbR | T cells, B cells | Peripheral lymph node development; proinflammatory |
OX40L | OX40 | Activated T cells, B cells, DCs, monocytes | Costimulatory; activation and migration of monocytes |
CD40L (CD154) | CD40 | T cells, monocytes, macrophages | Costimulatory; promotes T cell- dependent responses; B cell differentiation and class switching |
Fas-L | FAS | Activated T cells, B cells, and NK cells | Regulatory; pro apoptotic |
CD27L (CD70) | CD27 | Activated T cells, B cells, DCs, monocytes | Costimulatory |
CD30L (CD153) | CD30 | Neutrophils, B cells, macrophages, activated T cells | Costimulatory; promotes proliferation and cytokine production |
4-1BBL | 4-1BB | Activated T cells, B cells, dendritic cells, monocytes, macrophages | Costimulatory; promotes activation and migration of monocytes |
TRAIL | TRAIL-R1, R2, R3, and R4 | Activated NK cells, T cells | Costimulatory; promotes NK cell functions; proapoptotic |
RANK Ligand (TRANCE) | RANK receptor | T cells and osteoblasts | Costimulatory; promotes osteoclasto- genesis and cytokine production |
TWEAK | Fn14 | Monocytes, macrophages, endothelial | Proinflammatory; promotes cell growth for tissue repair and remodeling |
APRIL (TALL2) | TACI, BAFF-R, BCMA | Macrophages, dendritic cells | Promotes T cell independent responses; B cell homeostasis and differentiation |
BAFF (BlyS) | TACI, BAFF-R, BCMA | Macrophages, dendritic cells, astrocytes | B cell maturation and survival |
LIGHT | LTbR, DcR3, HVEM | Activated T cells, monocytes, dendritic cells | Costimulatory |
TL1A | DcR3, DR3 | Macrophages, endothelial cells | Promotes proliferation and cytokine production |
GITRL | GITR | Dendritic cells, macrophages, B cells, others | Costimulatory |
Colony stimulating factors (CSFs) are glycoproteins that bind to receptor proteins on the surfaces of hemopoietic stem cells, activating intracellular signaling pathways, then promoting production of white blood cells (mainly granulocytes such as neutrophils), in response to infection. In this section, we collect the source and function of several common CSFs on the table 4. Additionally, you can view the article named The Overview of Colony Stimulating Factors to obtain more information about CSFs.
Table 4. The Origin and Function of CSFs
Cytokine | Receptor | Source | Main Function |
---|---|---|---|
CSF1 | CSF1R | Monocytes and fibroblasts | Differentiation; prolifera- tion and survival |
CSF2 | CSF2RA | T cells, macrophages, and fibroblasts | Inflammatory; induction of activation; differ- entiation, growth, and survival |
CSF3 | CSF3R | Macrophages, fibroblasts, other tissues | Differentiation and activation of granulocytes |
What are Cytokines?
Cytokines and Diseases
Related Pathways
Related Articles