Type II Cytokine Family

Stimulation of cell growth, and production or inhibition of apoptosis, as well as affecting many immune mechanisms (Renauld, 2003 Pestka et al., 2004). Notably, IL-10 is a potent anti-inflammatory, immunomodulatory cytokine. The IFN system is an important contributor to innate immunity with IFN-y serving as a potent pro-inflammatory cytokine. The type II cytokine family is also comprised of both ThI and Th2 cytokines IFN-y is a ThI cytokine while IL-IO is a Th2 cytokine. 

Fig. 3.1 Families of cytokine receptors the cytokine receptors are classified into five major families immunoglobulin superfamily receptors, type I cytokine receptors, type II cytokine receptors, TNF-like receptors and chemokine receptors. The drawings illustrate their general biochemical structure (see Color Insert)...

The interferon receptor superfamily Cytokine receptor type II family Receptors for IFN-cx, -P, -y, IL-10... 

Studies have actually revealed two type I interferon receptor polypeptides. Sequence data from cloning studies place both in the class II cytokine receptor family. Both are transmembrane N-linked glycoproteins. Studies using isolated forms of each show that one polypeptide (called the a/p receptor) is capable of binding all type I interferons. The other one (the ap receptor) is specific for IFN-a-B (a specific member of the IFN-a family). Both receptors are present on most cell types. 

Among the most highly selective cytokine biopharmaceuticals are the interferons. Interferons are members of a large family of related proteins that may be divided into two categories type I and type II interferons. Type I interferons (i.e., a- and P-interferon) possess antiviral and anti-proliferative properties, whereas type II interferons (i.e., y-interferon) have immunostimulatory activity. Several animal species were examined for their responsiveness to interferons, and with the exception of nonhuman primates, all tested animal species were found to be unresponsive [15]. 

Some soluble products are secreted by cells of the immune system other than lymphocytes. For example, monocytes/macrophages are also capable of secreting cytokines, which are sometimes referred to as monokines and which include some interleukins, such as IL-1, IL-6, IL-8, and IL-12, and other factors such as tumor necrosis factor (TNF). Some soluble products with important roles in the immune system originate outside of the immune system. One example is interferon (IFN), which is actually a heterogeneous family of proteins of two types. Type I or viral IFNs are induced by infection and consists of IFN-a (interferon-a) and -IFN-)S, which are secreted by leukocytes, and fibroblasts or epithelial cells, respectively. Type II or immune IFN, consists of IFN-y, which is secreted by T cells (therefore, IFN-y can be classified as a lymphokine) in response to specific antigens. A second example of a soluble product which originates outside of the immune system is complement, which is primarily produced in the liver. Complement is actually a group of 20... 

IL-IOR is a single-chain receptor. IL-IOR belongs to the class II cytokine receptor family that also includes the IFN receptors (IFNy and IFNap receptors). The extracellular region consists of two homologous fibronectin type III domains that are without the WSXWS motif characteristic of class I cytokine receptors. It is expressed on B cells, thymocytes, and other cellular lines such as mast cells and macrophages. Human IL-IOR mRNA is restricted mostly to hematopoietic cells and cell lines. ... 

The first specifically binds IFNaB (IFNaS, a variety of IFNa) and is known as the IFNaB receptor. The second bmds both IFNa and IFNp and is called the IFNa/j3 receptor. The IFNapR is a member of the class II cytokine receptor family, which also includes the IFNyR, IL-IOR, and tissue factor. The IFNa/ R is also a class II cytokine receptor and contains at least two components that interact with type I IFNs, It is not known if these two receptors are expressed independently on the cell surface or are associated with each other in an IFN receptor complex. The receptors are present on most types of cells. A soluble form of the IFNa/pR has been identified in human serum and urine. 

The cytokines of the TG F/> family are the activating ligands for the family of TGF/ receptors. This comprises two subfamilies, the type I (T/>R-I) and type II (T/>R-II) receptors. These are transmembrane proteins composed of an extracellular ligand-binding domain, a single transmembrane element, and a cytoplasmic Ser/Thr kinase do-... 

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