IL-10 Family Ligand Review

IL-10 family of cytokines includes nine members, namely IL-10, IL-19, IL-20, IL-22, IL-24 (MDA-7), IL-26, and the more distantly related IL-28A, IL-28B, and IL-29. These cellular cytokines, as well as several cytokines encoded in viral genomes (viral cytokines), form a family of IL-10-related cytokines, the IL-10 family.

The interaction of these cytokines with their specific receptor molecules initiates a broad and varied array of signals that induce cellular antiviral states, modulate inflammatory responses, inhibit or stimulate cell growth, produce or inhibit apoptosis, and affect many immune mechanisms.

Below will briefly introduce each IL-10 family ligand and their functions, including interleukin-10, interleukin-19, interleukin-20, interleukin-22, interleukin-24 (MDA-7), interleukin-26 (AK155), interleukin-28 and interleukin-29.


Interleukin-10 (IL-10), the founding member of IL-10 family, was initially characterized as cytokine synthesis inhibitory factor (CSIF) from con A-stimulated Th2 cells that inhibited the production of cytokines such as IL-2, TNF-α, IFN-γ , and GM-CSF by Th1 cells, but not Th2 cells, in response to antigens presented by APC.

The IL-10 gene maps to a cytokine cluster that includes the genes IL-19, IL-20, IL-24, and IL-26 on chromosome 1q31-32. IL-10 is produced mainly by monocytes, T cells (mainly Tr1 cells), B cells, NK cells, macrophages, and DCs. Mast cells can also produce IL-10, which limits the rate of leukocyte infiltration, inflammation, and skin disorders such as contact dermatitis or after chronic ultraviolet B irradiation.

Biologically functional IL-10 exists in the form of a 36 kD homodimer composed of two non-covalently bonded monomers each with 160 amino acids length. Two disulfide bridges exist between the monomers, which are required for their biological activity and maintaining structural integrity. IL-10 targets various leukocytes and mainly represses excessive inflammatory responses. The receptor complex for IL-10 is made up of two IL-10R1 and two IL-10R2 chains.

IL-10 is a major regulator of innate immunity. It interferes with the production of inflammatory mediators by polymorphonuclear neutrophils, monocytes, and macrophages as well as upregulating the expression of molecules that amplify the anti-inflammatory effect of IL-10. This anti-inflammatory role is illustrated by interleukin-10-deficient mice that develop chronic inflammatory bowel disease owing to an inappropriate innate immune response to intestinal bacterial antigens.

IL-10 inhibits the expression of many proinflammatory cytokines, chemokines, and chemokine receptors and mediates allergen tolerance in allergen-specific immunotherapy and after exposure to high doses of allergen. IL-10 directly affects T-cell activation by suppressing CD28, CD2, and signaling of the inducible T-cell costimulator via the tyrosine phosphatase SHP-1.


As members of IL-10 family ligands, IL-19 was originally cloned by screening an Epstein-Barr virus (EBV)-transformed B cell library that contains a 534-bp open reading frame encoding a protein of 177 amino acids.

IL-19 shows ∼20% amino acid identity with IL-10, but it's very similar to IL-10 for having the helical structure. However, unlike IL-10 and like IL-20, IL-19 contains six conserved cysteine residues and functions as a monomer. IL-19 is located in chromosome 1q32 in an IL-10 family cluster.

Mouse IL-19 shows 71% amino acid identity to human IL-19. It contains 176 amino acids with a predicted signal peptide sequence of 24 amino acids. There are three potential N-linked glycoslysation sites in the mouse IL-19 gene. The genomic structure of mouse IL-19 is similar to that of human IL-19.

Although structurally IL-10 and IL-19 are similar molecules, the homologous region of IL-10 that interacts with IL-10R1 is much less conserved in IL-19, indicating that IL-19 does not interact with IL-10 receptors. IL-19 binds to a heterodimeric receptor made up of IL-20R1 and IL-20R2. This complex also binds IL-20 and IL-24.


The IL-20 cDNA is 925 bp long with an open reading frame of 531 bp encoding a putative polypeptide of 176 amino acids.

IL-20, contains both a signal sequence and one or more amphipathic helices commonly found in helical cytokines, such as IL-10. IL-20 shows 40%, 33%, and 28% amino acid identity to IL-19, IL-24/MDA-7, and IL-10, respectively, and therefore it was named IL-20.

Mouse IL-20 has 176 amino acids and shows 76% amino acid identity to human IL-20. Whereas IL-10 and IL-26 have four conserved cysteine residues, IL-19 and IL-20 contain six cysteine residues.

The formation of disulfide bonds between the extra cysteines in IL-20 would bring the hinge region of the molecule into close contact with the amino-terminus helix, thereby preventing the formation of an intercalating dimer.


IL-22, belongs to IL-10 family ligands. It consists of 179 amino acids, and shares 22% identity with IL-10.

Mouse IL-22 was identified as a gene specifically induced by IL-9 in mouse T cells, and the protein was originally designated IL-10-related T cell–derived inducible factor (IL-TIF). Activated human and mouse Th1 rather than Th2 CD4+ cells produce IL-22. Whereas there is a single copy of the IL-22 gene in the human genome and in genomes of BALB/c and DBA/2 mice, genomes of other mouse strains such as C57Bl/6, FVB, and 129 possess two IL-22 genes that were designated IL-22α and IL-22β.

The murine genes were mapped on chromosome 10 in the region of the IFN-γ gene. The human IL-22 gene is located on chromosome 12 about 90 Kb from the IFN-γ gene.

IL-22 is linked to allergy and asthma due to some genetic data.

Interleukin-24 (MDA-7)

Mda-7/IL-24 displays two distinct functions. At low concentration, Mda-7/IL-24 functions as a cytokine in normal cells. However, when Mda-7/IL-24 is overexpressed via an adenovirus-mediated gene delivery system it induces apoptosis selectively in cancer cells but not in normal cells.

Rat Mda-7/IL-24 contains 183 amino acid residues that shares 58.7% identity with human Mda-7/IL-24.

Due to Mda-7/IL-24 belongs to the IL-10 family ligands, it was predicted to exert its actions through cell-surface receptors. IL-10 family ligands signal through receptors that are dimers of an R1 type of receptor (with a long cytoplasmic domain) and an R2 type of receptor (with a short cytoplasmic domain).

Interleukin-26 (AK155)

IL-26/AK155 was upregulated in human T cells following infection with herpesvirus saimiri (HVS), with the capacity to transform these cells in culture.

The IL-26/AK155 cDNA consists of 1076 bp containing an 513 bp open reading frame of encoding a putative polypeptide of 171 amino acids that contains a predicted hydrophobic signal sequence 21 aa long. The IL-26/AK155 protein has 24.7% amino acid identity and 47% amino acid similarity to human IL-10. IL-26 contains six helices with four highly conserved cysteine residues that are assumed to be relevant for dimer formation as is the case in IL-10.

Interleukin-28 and Interleukin-29

IL-28 and IL-29, two novel members of the IL-10 family ligands, having low sequence identity with IL-10 (10%-13%). equence identity between IL-29 and IL-28A is 81%, and between IL-28A and IL-28B, 96%. They are important regulators of some of these processes, including antimicrobial/antiviral defense, wound healing, and removal of tumors.

The genes encoding human IL-28A, IL-28B, and IL-29 lay on chromosome 19q13.13. The mature polypeptides of IL-28A/IL-28B and IL-29 contain 175 and 181 amino acids respectively. IL-28A and IL-28B do not seem to be glycosylated, whereas IL-29 does.

IL-28A, IL-28B, and IL-29 share a common cellular receptor consisting of the cytokine receptor family class II members IL-28RA (also designated as IL-28R1 and IFN-λR1) and IL-10RB (also designated as IL-10R2).


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