Interleukin 7 (IL-7) is a protein [5] that in humans is encoded by the IL7 gene. [6] [7] [8]
IL-7 is a hematopoietic growth factor secreted by stromal cells in the bone marrow and thymus. It is also produced by keratinocytes, [9] dendritic cells, [10] hepatocytes, [11] neurons, and epithelial cells, [12] but is not produced by normal lymphocytes. [13] A study also demonstrated how the autocrine production of the IL-7 cytokine mediated by T-cell acute lymphoblastic leukemia (T-ALL) can be involved in the oncogenic development of T-ALL and offer novel insights into T-ALL spreading. [14]
The three-dimensional structure of IL-7 in complex with the ectodomain of IL-7 receptor has been determined using X-ray diffraction. [15]
IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoietic stem cells into lymphoid progenitor cells (as opposed to myeloid progenitor cells where differentiation is stimulated by IL-3).[ citation needed ] It also stimulates proliferation of all cells in the lymphoid lineage (B cells, T cells and NK cells).[ citation needed ] It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and homeostasis.[ citation needed ]
IL-7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development. [16] This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes.[ citation needed ] Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival. [17]
IL-7 binds to the IL-7 receptor, a heterodimer consisting of Interleukin-7 receptor alpha and common gamma chain receptor. [18] Binding results in a cascade of signals important for T-cell development within the thymus and survival within the periphery. Knockout mice which genetically lack IL-7 receptor exhibit thymic atrophy, arrest of T-cell development at the double positive stage, and severe lymphopenia. Administration of IL-7 to mice results in an increase in recent thymic emigrants, increases in B and T cells, and increased recovery of T cells after cyclophosphamide administration or after bone marrow transplantation.
IL-7 promotes hematological malignancies (acute lymphoblastic leukemia, T cell lymphoma). [19]
Elevated levels of IL-7 have also been detected in the plasma of HIV-infected patients. [20]
IL-7 as an immunotherapy agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and during HIV infection. [13] [21]
Recombinant IL-7 has been safely administered to patients in several phase I and II clinical trials. A human study of IL-7 in patients with cancer demonstrated that administration of this cytokine can transiently disrupt the homeostasis of both CD8+ and CD4+ T cells with a commensurate decrease in the percentage of CD4+CD25+Foxp3+ T regulatory cells. [22] No objective cancer regression was observed, however a dose limiting toxicity (DLT) was not reached in this study due to the development of neutralizing antibodies against the recombinant cytokine.
Associated with antiretroviral therapy, IL-7 administration decreased local and systemic inflammations in patients that had incomplete T-cell reconstitution. These results suggest that IL-7 therapy can possibly improve the quality of life of those patients. [23]
IL-7 could also be beneficial in improving immune recovery after allogenic stem cell transplant. [24]
Cytokines are a broad and loose category of small proteins important in cell signaling. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis.
Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein contains 152 amino acids and its molecular weight is 17 kDa. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells. The major function of IL-3 cytokine is to regulate the concentrations of various blood-cell types. It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors. It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching.
Interleukin 13 (IL-13) is a protein that in humans is encoded by the IL13 gene. IL-13 was first cloned in 1993 and is located on chromosome 5q31.1 with a length of 1.4kb. It has a mass of 13 kDa and folds into 4 alpha helical bundles. The secondary structural features of IL-13 are similar to that of Interleukin 4 (IL-4); however it only has 25% sequence identity to IL-4 and is capable of IL-4 independent signaling. IL-13 is a cytokine secreted by T helper type 2 (Th2) cells, CD4 cells, natural killer T cell, mast cells, basophils, eosinophils and nuocytes. Interleukin-13 is a central regulator in IgE synthesis, goblet cell hyperplasia, mucus hypersecretion, airway hyperresponsiveness, fibrosis and chitinase up-regulation. It is a mediator of allergic inflammation and different diseases including asthma.
Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the IL1B gene. There are two genes for interleukin-1 (IL-1): IL-1 alpha and IL-1 beta. IL-1β precursor is cleaved by cytosolic caspase 1 to form mature IL-1β.
Interleukin 16 is a pro-inflammatory pleiotropic cytokine. It's precursor, pro-interleukin-16 is a protein that in humans is encoded by the IL16 gene. This gene was discovered in 1982 at Boston University by Dr. David Center and Dr. William Cruikshank.
Interleukin 21 (IL-21) is a protein that in humans is encoded by the IL21 gene.
Interleukin 33 (IL-33) is a protein that in humans is encoded by the IL33 gene.
Interleukin-26 (IL-26) is a protein that in humans is encoded by the IL26 gene.
Intraepithelial lymphocytes (IEL) are lymphocytes found in the epithelial layer of mammalian mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract. However, unlike other T cells, IELs do not need priming. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT).
T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to actually inhibit Treg differentiation. However, Th17s are developmentally distinct from Th1 and Th2 lineages. Th17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces; such protective and non-pathogenic Th17 cells have been termed as Treg17 cells.
Interleukin-12 subunit alpha is a protein that in humans is encoded by the IL12A gene.
G protein-coupled receptor 15 is a protein that in humans is encoded by the GPR15 gene.
Single Ig IL-1-related receptor (SIGIRR), also called Toll/Interleukin-1 receptor 8 (TIR8) or Interleukin-1 receptor 8 (IL-1R8), is transmembrane protein encoded by gene SIGIRR, which modulate inflammation, immune response, and tumorigenesis of colonic epithelial cells.
Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene.
The Interleukin-2 receptor alpha chain is a protein involved in the assembly of the high-affinity Interleukin-2 receptor, consisting of alpha (IL2RA), beta (IL2RB) and the common gamma chain (IL2RG). As the name indicates, this receptor interacts with Interleukin-2, a pleiotropic cytokine which plays an important role in immune homeostasis.
Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 consists of a heterodimer between IL-12Rβ1 and IL-23R.
Type 3 innate lymphoid cells (ILC3) are immune cells from the lymphoid lineage that are part of the innate immune system. These cells participate in innate mechanisms on mucous membranes, contributing to tissue homeostasis, host-commensal mutualism and pathogen clearance. They are part of a heterogeneous group of innate lymphoid cells, which is traditionally divided into three subsets based on their expression of master transcription factors as well as secreted effector cytokines - ILC1, ILC2 and ILC3.
Th22 cells are subpopulation of CD4+ T cells that produce interleukin-22 (IL-22). They play a role in the protective mechanisms against variety of bacterial pathogens, tissue repair and wound healing, and also in pathologic processes, including inflammations, autoimmunity, tumors, and digestive organs damages.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.