Cytokine is a low-molecular-weight soluble protein (5–20 kDa) induced by immunogens, mitogens or other stimulants in a variety of cells. Many studies have revealed that cytokines are involved in autocrine, paracrine and endocrine signaling as immunomodulating agents (Figure 1). The classification of cytokine is generally based on two principles, structure and function. Here, the classification of cytokine family is based on the structure of cytokine. So what is cytokine family? What are the main types of cytokine family?
Figure 1. The Properties of Cytokines
What is Cytokine Family?
Cytokine family refers a series of cytokines that share sequence similarity and exhibit homology and some promiscuity in their reciprocal receptor systems. However, it doesn’t mean that they exhibit functional similarity. Cytokine families also contain important regulatory cell membrane receptor-ligand pairs. They reflect evolutionary pressures that use common structural motifs in diverse immune functions in higher mammals. Taking the IL-1/IL-1 receptor superfamily as an example, IL-1/IL-1 receptor superfamily contains cytokines, including IL-1β, IL-1α, IL-receptor antagonist, IL-18, and IL-33, which mediate physiologic and host-defense function, but this family also includes the Toll-like receptors, a series of mammalian pattern-recognition molecules with a crucial role in recognition of microbial species early in innate responses.
What are The Main Types of Cytokine Family?
Generally speaking, cytokine families include interleukin family, interferon family, tumor necrosis factor (TNF) superfamily, and chemokines superfamily. Among of them, interleukin superfamily can be divided into several cytokine superfamiies based on different function, involving IL-1 family, IL-6 family and IL-17 family, etc.
Interleukin is a kind of cytokines, which plays a critical role in immunological regulation and homeostasis. It is originally discovered from leukocytes. But now, it is found to be produced by a lot of cells including macrophages, lymphocytic cells with a solid structure and function. Interleukin superfamily includes a large number of cytokines which are named IL-1~IL-38. As mentioned above, these ILs can be further divided into several sub-families.
Such as IL-1 family, The IL-1 superfamily has 11 members, which have similar gene structure, although originally it contained only four members IL-1α, IL-1β, IL-1Ra and IL-18. They play a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
Interferons (IFNs) are a family of mammalian cytokines initially characterized by their ability to "interfere" with viral replication by protecting cells from virus infections. The IFN family is consist of three main classes of cytokines, type I IFNs, type II IFN and type III IFN. Among of them, type I IFN and type II IFN are well-studied.
Such as type I interferon includes interferon α(which can be further divided into 13 different subtypes(IFN-α1, -α2, -α4, -α5, -α6, -α7, -α8, -α10, -α13, -α14, -α16, -α17 and -α21), β, ε, к, and ω in human. All type I IFNs bind a identical common cell-surface receptor, which is known as the type I IFN receptor. More information about interferon>>
TNF superfamily is a protein superfamily of type II transmembrane proteins containing TNF homology domain and forming trimers. Members of this superfamily can be released from the cell membrane by extracellular proteolytic cleavage and function as a cytokine. These proteins are expressed predominantly by immune cells and they regulate diverse cell functions, including immune response and inflammation, but also proliferation, differentiation, apoptosis and embryogenesis. Based on sequence, function, and structural similarities, the superfamily contains 19 members that bind to 29 members of TNF receptor superfamily. More information about TNF superfamily>>
Chemokines are a group of cytokines with small molecular weight whose main action is the recruitment of leukocyte subsets under homeostatic and pathological conditions.
Through interacting with chemokine receptors that are expressed on the cell surface as 7-transmembrane proteins coupled with G-protein for signaling transduction, chemokine can induce firm adhesion of targeted cells to the endothelium and direct the movement of targeted cells to their destination according to the concentration gradient of a given chemokine. According to behavior and structural characteristics, the chemokine family consists of 50 endogenous chemokine ligands in humans and mice. More information about chemokine family>>