Interleukin-36 gamma previously known as interleukin-1 family member 9 (IL1F9) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''IL36G''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Expression
''IL36G'' is well-expressed in the epithelium of the skin, gut, and lung. In the skin ''IL36G'' is predominantly expressed in epidermal granular layer keratinocytes with little to no expression in basal layer keratinocytes.
Function
The protein encoded by this gene is a member of the
interleukin-1
The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
Discovery
Discovery of these cytokines began with studies on t ...
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
family. This gene and eight other interleukin-1 family genes form a cytokine gene cluster on chromosome 2. The activity of this cytokine is mediated via the interleukin-1 receptor-like 2 (
IL1RL2
Interleukin-1 receptor-like 2 is a protein that in humans is encoded by the ''IL1RL2'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA t ...
/IL1R-rp2/IL-36 receptor), and is specifically inhibited by interleukin-36 receptor antagonist, (
IL-36RA/IL1F5/IL-1 delta).
Interferon-gamma
Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. ...
,
tumor necrosis factor-alpha
Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...
and interleukin-1 β (
IL-1β
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."Catabolin" ...
) are reported to stimulate the expression of this cytokine in
keratinocyte
Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...
s. The expression of this cytokine in keratinocytes can also be induced by a multiple Pathogen-Associated Molecular Patterns (
PAMPs
Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes, but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both p ...
). Both IL-36γ mRNA and protein have been linked to psoriasis lesions and has been used as a biomarker for differentiating between eczema and psoriasis. As with many other interleukin-1 family cytokines IL-36γ requires proteolytic cleavage of its N-terminus for full biological activity. However, unlike IL-1β the activation of IL-36γ is
inflammasome
Inflammasomes are cytosolic multiprotein complexes of the innate immune system responsible for the activation of inflammatory responses and cell death. They are formed as a result of specific cytosolic pattern recognition receptors (PRRs) sens ...
-independent. IL-36γ is specifically cleaved by the endogenous protease
cathepsin S
Cathepsin S is a protein that in humans is encoded by the ''CTSS'' gene. Transcript variants utilizing alternative polyadenylation signals exist for this gene.
Cathepsin S is a member of the peptidase C1 family of cysteine cathepsins, a lysosom ...
as well exogenous proteases derived from fungal and bacterial pathogens.
References
Biomarkers
Further reading
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{{Interleukin receptor modulators