Interleukin 7
Encyclopedia
IL-7 a hematopoietic
growth factor
secreted by stromal cell
s in the red marrow and thymus
. It is also produced by keratinocyte
s, dendritic cell
s, hepatocyte
s, neuron
s, and epithelial cells but is not produced by lymphocyte
s.
that in humans is encoded by the IL7 gene
.
s into lymphoid progenitor cells (as opposed to myeloid progenitor cells where differentiation is stimulated by IL-3
). It also stimulates proliferation of all cells in the lymphoid lineage (B cell
s, T cell
s and NK cells
). It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and homeostasis
.
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 (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cell
s, and may serve as a regulatory factor for intestinal mucosal lymphocytes. Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.
, a heterodimer consisting of Interleukin-7 receptor alpha and common gamma chain receptor. 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.
.
agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and during HIV infection
.
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. 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.
(Selzentry - ViiV Healthcare) for the treatment of HIV infections. It is hoped that by combining the antiretroviral drugs, coupled with an immunomodulating agent capable of targeting or inducing activation of latently infected cells, the reservoirs of HIV can be decreased and, in the best case scenario, eradication of the virus may be feasible.
Haematopoiesis
Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells...
growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
secreted by stromal cell
Stromal cell
In cell biology, stromal cells are connective tissue cells of any organ, for example in the uterine mucosa , prostate, bone marrow, and the ovary. They are cells that support the function of the parenchymal cells of that organ...
s in the red marrow and thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
. It is also produced by keratinocyte
Keratinocyte
Keratinocytes are the predominant cell type in the epidermis, the outermost layer of the human skin, constituting 95% of the cells found there. Those keratinocytes found in the basal layer of the skin are sometimes referred to as "basal cells" or "basal keratinocytes"...
s, dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
s, hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...
s, neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s, and epithelial cells but is not produced by lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s.
Genetics
Interleukin 7 (IL7) is a proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the IL7 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
T cell maturation
IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoietic stem cellStem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s into lymphoid progenitor cells (as opposed to myeloid progenitor cells where differentiation is stimulated by IL-3
Interleukin 3
Interleukin 3, also known as IL-3, is a protein that in humans is encoded by the IL3 gene.-Function:Interleukin-3 is an interleukin, a type of biological signal that can improve the body's natural response to disease as part of the immune system...
). It also stimulates proliferation of all cells in the lymphoid lineage (B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s, T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s and NK cells
Natural killer cell
Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
). It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
.
IL-7 is a cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
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 (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cell
Goblet cell
Goblet cells are glandular simple columnar epithelial cells whose sole function is to secrete mucin, which dissolves in water to form mucus. They use both apocrine and merocrine methods for secretion....
s, and may serve as a regulatory factor for intestinal mucosal lymphocytes. Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.
IL-7 signaling
IL-7 binds to the IL-7 receptorInterleukin-7 receptor
The interleukin-7 receptor is a protein found on the surface of cells. It is made up of two different smaller protein chains - i.e. it is a heterodimer, and consists of two subunits, interleukin-7 receptor-α and common-γ chain receptor . The common-γ chain receptors is shared with various...
, a heterodimer consisting of Interleukin-7 receptor alpha and common gamma chain receptor. 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
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
, 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
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
administration or after bone marrow transplantation.
Cancer
Il-7 promotes hematological malignacies (acute lymphoblastic leukemia, T cell lymphoma).Viral Infections
Elevated levels of IL-7 have also been detected in the plasma of HIV-infected patientsHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
.
Clinical application
IL-7 as an immunotherapyImmunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and during HIV infection
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
.
Cancer
RecombinantRecombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
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
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
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. 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.
HIV infection
Cytheris has initiated the Phase II clinical trial of recombinant human IL-7, in combination with two antiretroviral drugs, integrase inhibitor raltegravir (Isentress - Merck & Co) and the CCR5 inhibitor, maravirocMaraviroc
Maraviroc is an antiretroviral drug in the CCR5 receptor antagonist class used in the treatment of HIV infection. It is also classed as an entry inhibitor.-Mechanism of action:...
(Selzentry - ViiV Healthcare) for the treatment of HIV infections. It is hoped that by combining the antiretroviral drugs, coupled with an immunomodulating agent capable of targeting or inducing activation of latently infected cells, the reservoirs of HIV can be decreased and, in the best case scenario, eradication of the virus may be feasible.