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Interleukin (IL) superfamily

What is the IL gene family/factors?

IL superfamily, a member of larger group cytokines, is consisting of proteins called interleukins and interleukin receptors. IL superfamily members involve with variety of processes, including immunity, inflammation, and the formation of blood cells. IL superfamily members promote the growth of immune system cells and help regulate the immune system. The subfamilies of IL superfamily include IL-1 subfamily, IL-6 subfamily, IL-10 subfamily, IL-12 subfamily, IL-17 subfamily and other interleukins or receptors. Till now, 43 different IL family members have been identified according to HGNC. Most interleukins are named with "IL" followed by one or more numbers and letters (for example, IL12B) so that interleukin receptors have similar names. What’s more, they are also followed with "R" to show that they are receptor proteins (such as IL36RN).

Interleukins are secreted by several types of cells, mainly about immune system cells T-lymphocytes and B-lymphocytes. Interleukins function by binding to interleukin receptors, which are embedded in the outer cell membranes. Once an interleukin binds to its receptor, a series of chemical signals within the cell that regulate various cell functions are triggered.

IL and IL receptors are related to many diseases, particularly in immune system like autoimmune diseases. Autoimmune diseases occur when the host immune system is inappropriately directed against self-antigens. For example, the role of IL18 in most autoimmune diseases is the facilitator in which high levels of extracellular IL18 correlate well with the disease progression. These high levels of IL18 have a pleiotropic effect on immune cells with the sustained production of IFN γ and increased cytotoxicity of Natural Killer (NK) cells, resulting in tissue damage and necrosis. Moreover, researchers are studying interleukins for cancer therapy.

Interleukins function

Interleukins (IL) members function in many physiological processes, especially in immunity. Here we introduce the functions of some interleukins.

IL1 family agonist cytokines do not stimulate the immune response directly but indirectly through other cytokines and effector proteins that are upregulated with increasing levels of these agonists.

Interleukin-2 (IL 2) is one of the key growth-regulating cytokines for T cells. It was discovered as a “T cell growth factor” from conditioned media that promoted growth of T lymphocytes from the bone marrow. IL 2 performs at least four critical functions to activate and regulate homeostasis of T-cells.

IL 3 can stimulate the hematopoietic stem cells into myeloid progenitor cells. If combining with IL 7, IL 3 stimulates hematopoietic stem cells into lymphoid progenitor cells. In addition, IL 3 stimulates proliferation of all cells in the myeloid lineage functioning with other cytokines.

IL 4 involves with many biological processes, for instance, the stimulation of activated B-cell and T-cell proliferation. IL 4 is also an important participant in humoral and adaptive immunity. IL 4 decreases the production of some cells such as Th1 cells, macrophages, IFN-gamma and dendritic cell.

IL 5 plays a key role in stimulating B cell growth and increasing immunoglobulin secretion. IL 5 also mediates eosinophil activation.

IL 6 is a key mediator in diseases like fever and acute phase response. IL 6 can overcome the blood-brain barrier and activate PGE2 expression in the hypothalamus leading to change the body's temperature setpoint.

IL 8 induces chemotaxis of target cells migrating toward the site of infection. What’s more, phagocytosis is also induced by IL 8. In target cells, IL 8 induces a series of physiological responses for migration and phagocytosis, for example, increase of intracellular Ca2+, and the respiratory burst.

IL 10 family functions with multiple effects in immune regulation and inflammation. IL 10 can decrease the expression of Th1 cytokines and MHC class II antigens. IL 10 also promotes B cell survival, proliferation and antibody production. IL 10 involves in the regulation of the JAK-STAT signaling pathway, as well.

IL 18 is involved in both innate and adaptive immune responses and it is analogous to the IL1 family in many ways.

IL33 family is principally involved in Th2-mediated immune responses such as asthma, allergy-induced inflammation, and parasitic infections.

IL12 receptors
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