Interleukin 15
Encyclopedia
Interleukin 15 is a cytokine
with structural similarity to IL-2
. Like IL-2
, IL-15 binds to and signals through the IL-2/IL-15 beta chain (CD122) and the common gamma chain (gamma-C, CD132). IL-15 is secreted by mononuclear phagocytes (and some other cells) following infection by virus
(es). This cytokine induces cell proliferation of natural killer cell
s; cells of the innate immune system
whose principal role is to kill virally infected cells.
.
and natural killer
(NK) cell activation and proliferation. Survival signals that maintain memory T cells in the absence of antigen are provided by IL-15. This cytokine is also implicated in NK cell development. In rodent lymphocytes, IL-15 prevents apoptosis
by inducing an apoptosis inhibitor, BCL2L1
/BCL-x(L). In humans with celiac disease
IL-15 similarly suppresses apoptosis in T-lymphocytes by inducing Bcl-2
and/or Bcl-xL
.
A hematopoietin
receptor, the IL-15 receptor, that binds IL-15 propagates its function. Some subunits of the IL-15 receptor are shared in common with the receptor for a structurally related cytokine called interleukin 2
(IL-2) allowing both cytokines to compete for and negatively regulate each other's activity. CD8
+ memory T cell number is controlled by a balance between IL-15 and IL-2. When IL-15 binds its receptor, JAK kinase
, STAT3
, STAT5
, and STAT6
transcription factor
s are activated to elicit downstream signaling events.
(the syndrome associated with primary Epstein-Barr virus
infection), IL-15R expressing lymphocytes are not detected--even 14 years after infection.
of IL-15 in patients with metastatic
melanoma
and renal cell carcinoma
(kidney cancer) has begun to enroll patients at the National Institutes of Health
.
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...
with structural similarity to IL-2
Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
. Like IL-2
Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
, IL-15 binds to and signals through the IL-2/IL-15 beta chain (CD122) and the common gamma chain (gamma-C, CD132). IL-15 is secreted by mononuclear phagocytes (and some other cells) following infection by virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
(es). This cytokine induces cell proliferation of natural killer cell
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...
s; cells of the innate immune system
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
whose principal role is to kill virally infected cells.
Gene
Two alternatively spliced transcript variants of this gene encoding the same protein have been reported. In humans, interleukin 15 is encoded by the IL15 geneGene
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...
.
Function
Interleukin 15 (IL-15) regulates TT 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...
and natural killer
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...
(NK) cell activation and proliferation. Survival signals that maintain memory T cells in the absence of antigen are provided by IL-15. This cytokine is also implicated in NK cell development. In rodent lymphocytes, IL-15 prevents apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
by inducing an apoptosis inhibitor, BCL2L1
BCL2-like 1 (gene)
Bcl-2-like protein 1 is a protein that in humans is encoded by the BCL2L1 gene.-Interactions:BCL2-like 1 has been shown to interact with RAD9A, RTN1, BAK1, Reticulon 4, Bcl-2-associated X protein, BCAP31, Bcl-2-interacting killer, PPP1CA, Noxa, VDAC1, BCL2L11, Bcl-2-associated death promoter,...
/BCL-x(L). In humans with celiac disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
IL-15 similarly suppresses apoptosis in T-lymphocytes by inducing Bcl-2
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
and/or Bcl-xL
Bcl-xL
B-cell lymphoma-extra large is a transmembrane molecule in the mitochondria. It is involved in the signal transduction pathway of the FAS-L. It is one of several anti-apoptotic proteins which are members of the Bcl-2 family of proteins. It has been implicated in the survival of cancer cells. Other...
.
A hematopoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
receptor, the IL-15 receptor, that binds IL-15 propagates its function. Some subunits of the IL-15 receptor are shared in common with the receptor for a structurally related cytokine called interleukin 2
Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
(IL-2) allowing both cytokines to compete for and negatively regulate each other's activity. CD8
CD8
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
+ memory T cell number is controlled by a balance between IL-15 and IL-2. When IL-15 binds its receptor, JAK kinase
Janus kinase
Janus kinase is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 & 2 , but were ultimately published as "Janus kinase"...
, STAT3
STAT3
Signal transducer and activator of transcription 3 also known as STAT3 is a transcription factor which in humans is encoded by the STAT3 gene.- Function :The protein encoded by this gene is a member of the STAT protein family...
, STAT5
STAT5
STAT5 refers to two highly related proteins, STAT5A and STAT5B, which are encoded by separate genes, but are 90% identical at the amino acid level....
, and STAT6
STAT6
STAT6 is a human gene. The protein encoded by this gene is a member of the STAT family of transcription factors.In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell...
transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s are activated to elicit downstream signaling events.
Epstein-Barr Virus
In humans with history of acute infectious mononucleosisInfectious mononucleosis
Infectious mononucleosis is an infectious, widespread viral...
(the syndrome associated with primary Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
infection), IL-15R expressing lymphocytes are not detected--even 14 years after infection.
Metastatic Cancer
IL-15 has been shown to enhance the anti-tumor immunity of CD8+ T cells in pre-clinical models. A phase I clinical trial to evaluate the safety, dosing, and anti-tumor efficacyEfficacy
Efficacy is the capacity to produce an effect. It has different specific meanings in different fields. In medicine, it is the ability of an intervention or drug to reproduce a desired effect in expert hands and under ideal circumstances.- Healthcare :...
of IL-15 in patients with metastatic
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
and renal cell carcinoma
Renal cell carcinoma
Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...
(kidney cancer) has begun to enroll patients at the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
.