Generated using OpenAI Deep Research API
Interleukin-22 (IL-22) is a secreted cytokine in the IL-10 family that plays a pivotal role in modulating immune responses at barrier surfaces (www.ncbi.nlm.nih.gov) (www.genecards.org). Unlike many cytokines, IL-22 primarily acts on non-immune cells (e.g. epithelial cells and hepatocytes) to induce protective and regenerative programs, rather than directly on immune cells (www.genecards.org). IL-22 binds to a heterodimeric receptor complex composed of IL-22RA1 (a cell-type specific α-chain on epithelial and stromal cells) and the shared IL-10RB (IL-10R2) β-chain (www.genecards.org). Upon ligand binding, this receptor activates the JAK1 and TYK2 tyrosine kinases, leading to phosphorylation of STAT3 and downstream signaling via the ERK, PI3K/AKT, and STAT3 pathways (www.genome.jp) (www.genecards.org). These signaling cascades promote target cell survival, proliferation, and repair, enabling tissues to withstand and recover from inflammatory damage (www.genome.jp) (www.genecards.org). IL-22’s mechanism is distinctive in that it has no direct effect on hematopoietic cells, focusing its action on tissue cells at sites of inflammation (www.genecards.org). A unique regulatory aspect of IL-22 biology is the presence of a soluble IL-22 binding protein (IL-22BP, encoded by IL22RA2) that acts as a decoy receptor – IL-22BP can sequester IL-22 and prevent it from signaling, thus buffering IL-22 activity in tissues (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). This IL-22/IL-22BP system allows tight control of IL-22-driven pathways, balancing host defense and tissue damage during immune responses.
Subcellular localization: IL-22 is a secreted protein. It contains an N-terminal signal peptide (amino acids 1–33) that directs it into the endoplasmic reticulum/Golgi secretory pathway, after which the mature cytokine is released into the extracellular space (www.genome.jp) (www.genome.jp). Consequently, the functional location of IL-22 is the extracellular region, where it diffuses to interact with receptors on target cell surfaces. IL-22 is typically found in the extracellular milieu (outside the cell) and is not associated with intracellular organelles or the plasma membrane (except during the secretion process) (www.proteinatlas.org) (www.genome.jp). Consistent with this, Reactome and other pathway databases localize IL-22 to the extracellular region in human pathways (reactome.org). Its receptor subunits IL-22RA1 and IL-10RB are membrane-bound on responsive cells, allowing IL-22 to exert effects in a paracrine manner.
Protein structural features: The IL-22 protein is 179 amino acids in length (precursor form), with the first 33 residues constituting a signal peptide and residues 34–179 comprising the mature cytokine chain (www.genome.jp). It belongs to the class II α-helical cytokine family (the IL-10 family) which share a characteristic four-helix bundle fold (pmc.ncbi.nlm.nih.gov) (www.genome.jp). Indeed, IL-22 is structured as a compact bundle of six α-helices (A–F), of which four (A, C, D, F) form the canonical helical bundle common to IL-10-related cytokines (pmc.ncbi.nlm.nih.gov). Unlike IL-10 (which forms a homodimer), IL-22 functions as a monomeric cytokine, consistent with crystal structures of IL-22 that show it does not form intertwined dimers (pmc.ncbi.nlm.nih.gov). The IL22 protein domain (Pfam: IL22, residues ~40–179) is also known as IL-TIF domain, reflecting its original name “IL-10-related T-cell inducible factor” (www.ncbi.nlm.nih.gov).
IL-22 contains several post-translational features important for its stability and function. It is a glycoprotein with N-linked glycosylation sites at Asn-54 and Asn-97 (experimentally confirmed) and another predicted site at Asn-68 (www.genome.jp). These glycans, also observed in crystal structures, decorate the surface of IL-22 and can influence receptor binding and protein half-life (pmc.ncbi.nlm.nih.gov). IL-22 is further stabilized by two conserved disulfide bonds (Cys-40 to Cys-132, and Cys-89 to Cys-178) that tether its helices together (www.genome.jp) (pmc.ncbi.nlm.nih.gov). These disulfide bridges are critical for maintaining the proper fold of IL-22 as a soluble cytokine. Overall, the domain architecture and cysteine connectivity of IL-22 mirror those of other IL-10 family cytokines, underscoring a preserved structural framework. Notably, structural studies (including X-ray crystallography of human and zebrafish IL-22) have shown IL-22 adopts the typical class-II cytokine architecture, confirming that its 3D structure is highly conserved across species (pubmed.ncbi.nlm.nih.gov).
IL-22 is deeply involved in innate and adaptive immune processes, especially at mucosal and barrier tissues. As a cytokine primarily acting on epithelial and tissue cells, IL-22 serves as a key mediator of the innate immune response (GO:0045087) and the inflammatory response (GO:0006954) during infection and injury (www.ncbi.nlm.nih.gov). One of its hallmark functions is to promote antimicrobial defense at mucosal surfaces – IL-22 stimulates epithelial cells (in the skin, gut, lung, etc.) to produce antimicrobial peptides (such as β-defensins, S100 proteins, Reg3 lectins in mice) and mucus, thereby strengthening the barrier against pathogenic bacteria and fungi (www.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This activity places IL-22 in the category of cytokines driving defense response to bacterium (GO:0042742) and other microbes as part of the immune system’s first line of defense. For example, IL-22 from Th17 cells or ILC3 cells can induce colon epithelial cells to secrete antibacterial proteins and thus limit bacterial translocation during gut infections (pmc.ncbi.nlm.nih.gov).
In parallel, IL-22 is crucial for tissue repair and regenerative processes. It promotes proliferation and survival of epithelial cells, aiding in wound healing of damaged tissues (www.genecards.org) (www.genome.jp). Upon injury or inflammation, IL-22 signaling helps maintain or restore the integrity of tissue barriers: it encourages epithelial cell growth (GO:0050673) and tissue regeneration (e.g., aiding wound healing, GO:0042060) to fill in damaged areas (www.genecards.org) (pmc.ncbi.nlm.nih.gov). For instance, IL-22 has been shown to drive intestinal stem cell proliferation and epithelial regeneration after acute injury in the gut, largely via STAT3 activation in those cells (www.genecards.org). In the skin, IL-22 causes keratinocytes to hyper-proliferate and migrate, which is helpful for closing wounds (but can contribute to psoriatic pathology when unregulated). In the liver, IL-22 protects hepatocytes from damage and supports their regeneration (as observed in mouse models of liver injury) (pmc.ncbi.nlm.nih.gov). Thus, IL-22 serves a dual role: pro-inflammatory and protective, orchestrating both the immune defense (GO:0006955) against pathogens and the rebuilding of tissue post-damage.
IL-22 often acts in concert with other cytokines and cells. It is a signature effector of the Th17/IL-23 axis: IL-22 production is induced by IL-23 and is typically co-expressed with IL-17A/F in Th17 responses, though IL-22 can also be produced independently by other cell types (pmc.ncbi.nlm.nih.gov). The combined actions of IL-17 and IL-22 are important in conditions like mucosal candidiasis and certain bacterial infections, where IL-17 mobilizes neutrophils and IL-22 fortifies epithelial defenses. In barrier immunity, IL-22’s role is largely protective, helping contain infection and prevent pathogen dissemination (pmc.ncbi.nlm.nih.gov). However, IL-22 can also have pro-inflammatory properties (www.ncbi.nlm.nih.gov) – for example, by sustaining chronic inflammation in autoimmune diseases (discussed below). Importantly, IL-22’s effects are context-dependent: in an environment with ongoing infection or tissue stress, IL-22 is generally beneficial (enhancing antimicrobial immunity and repair), but in an already inflamed tissue without active infection, continual IL-22 signaling may contribute to pathogenic inflammation. The JAK-STAT pathway (particularly STAT3) is the central pathway triggered by IL-22, linking this cytokine to numerous gene expression programs involved in inflammation, cell survival (e.g. upregulating Bcl-2/Bcl-x_L), and proliferation (www.genome.jp) (www.genecards.org). There is also evidence IL-22 can activate ERK and AKT pathways, meaning it can cross-talk with growth factor signaling to some extent (www.genome.jp). Through these pathways, IL-22 influences a broad set of biological processes, from acute phase responses in the liver (www.genome.jp) to epithelial cell migration (IL-22 was shown to promote epithelial cell spreading and mobility) (www.genome.jp). Overall, IL-22 occupies a unique niche in the immune system: it is an immune mediator that primarily acts on tissues, making it crucial for the crosstalk between the immune system and barrier organ function.
Cell type expression: IL22 gene expression is normally tightly regulated and is low or undetectable in most resting tissues (www.ncbi.nlm.nih.gov). Under homeostatic conditions, IL-22 mRNA shows a tissue-enhanced pattern predominantly in immune-related sites. RNA profiling indicates highest IL22 expression in lymphoid tissues (such as tonsils, lymph nodes) and in certain barrier organs like the skin and digestive tract, while most other tissues have little to no IL-22 expression (v20.proteinatlas.org). The Human Protein Atlas reports IL22 as “detected in some tissues” with enrichment in lymphoid tissue and urinary bladder (v20.proteinatlas.org). This suggests that IL-22 is not a ubiquitously expressed cytokine but is present in specific contexts – likely produced by immune cells residing in or homing to those tissues.
Cellular sources: The primary producers of IL-22 are activated CD4⁺ T helper cells (notably the Th17 subset, and a related subset sometimes called Th22) and innate lymphoid cells (especially group 3 ILCs, which include lymphoid tissue inducer cells and NK-like cells in mucosal tissues) (pmc.ncbi.nlm.nih.gov). During an immune response, Th17 cells differentiate (under IL-6, TGF-β and IL-1β signals) and, upon stimulation with IL-23, secrete high levels of IL-22 along with IL-17 (pmc.ncbi.nlm.nih.gov). There are also specialized NK-like cells that produce IL-22; for example, NKp46⁺ ILC3 cells in the gut mucosa constitutively express IL-22 or rapidly produce it in response to microbial cues (pmc.ncbi.nlm.nih.gov). In human tonsils and Peyer’s patches, an “NK-22” cell subset (CD56⁺ NK cells) has been described that releases IL-22 when stimulated by IL-23 (pmc.ncbi.nlm.nih.gov). Other cell types that can produce IL-22 include γδ T cells, mucosal-associated invariant T (MAIT) cells, and neutrophils (the latter only under certain inflammatory conditions). Notably, dendritic cells and macrophages do not produce IL-22 – instead, they produce IL-23 and other cytokines that stimulate IL-22 production by lymphocytes.
Inducing signals: The expression of IL22 is induced during inflammatory and infectious conditions. IL-23 is the most potent cytokine for inducing IL-22; it drives IL-22 production from both T cells and ILC3s in the context of infections like bacteria (e.g. Citrobacter rodentium infection in mice triggers an IL-23 → IL-22 axis for gut defense) (pmc.ncbi.nlm.nih.gov). Additionally, pro-inflammatory signals such as IL-1β and TNF-α can synergize to enhance IL-22 output from T cells. Microbial products (via dendritic cells) lead to an IL-23-rich environment, which in turn causes a surge in IL-22 from responding lymphocytes (pmc.ncbi.nlm.nih.gov). This is often seen in mucosal infections: for example, during a bacterial infection at mucosal surfaces, IL-22 gene expression is rapidly upregulated in Th17/ILC3 cells as part of the innate defense mechanism (pmc.ncbi.nlm.nih.gov). Conversely, anti-inflammatory cytokines like IL-10 or regulatory T cells can suppress IL-22 production. The IL22 gene itself is under transcriptional control of factors such as aryl hydrocarbon receptor (AHR) (known to enhance IL-22 in Th17/IL-22-producing cells) and is also influenced by STAT3 (downstream of IL-23 signaling in the IL-22-producing cell).
Regulation and feedback: Because IL-22 can be double-edged, its activity is often counter-regulated. IL-22-producing cells co-express IL-22BP in some contexts: for instance, certain dendritic cells in gut produce IL-22BP to bind IL-22 as a feedback inhibitor. Retinoic acid in the gut environment upregulates IL-22BP, dampening IL-22 to prevent excessive epithelial proliferation. On the other hand, during acute infection, IL-22BP expression is suppressed to allow IL-22 to exert its protective effect. Thus, IL22 expression and action are controlled at multiple levels – transcriptional induction by cytokines (IL-23, etc.), and post-secretory neutralization by IL-22BP. In summary, IL-22 is mainly expressed during immune challenge by specific immune cell subsets, and its production is a hallmark of Th17/ILC3-driven inflammation. Baseline expression in healthy conditions is generally low, highlighting IL-22’s role as an “on-demand” mediator in immunity.
Given its role at the interface of immunity and tissue integrity, IL-22 has been implicated in a variety of diseases, especially those involving chronic inflammation or barrier dysfunction. Dysregulated IL-22 – whether excessive or insufficient – can contribute to pathology.
Inflammatory and Autoimmune Diseases: IL-22 is a key effector in several autoimmune or autoinflammatory conditions. High IL-22 levels are found in psoriasis, rheumatoid arthritis, inflammatory bowel disease (IBD) (such as Crohn’s disease and ulcerative colitis), and psoriatic arthritis (pmc.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov). In psoriasis, IL-22 is produced by skin-homing Th17/Th22 cells and drives keratinocyte proliferation and acanthosis (thickening of the epidermis). A mouse study demonstrated that IL-22 is required for Th17-mediated psoriatic skin inflammation – animals lacking IL-22 were protected from developing skin lesions (pmc.ncbi.nlm.nih.gov). This establishes IL-22 as a pathological driver in psoriasis-like disease, making it a potential therapeutic target. In rheumatoid arthritis, IL-22 is elevated in patient sera and synovial fluid and may contribute to joint inflammation and pannus formation (by inducing matrix metalloproteinases and proliferating synovial fibroblasts). In IBD, IL-22 plays a paradoxical role: it is generally protective for the intestinal mucosa (promoting wound healing and mucus production), but overproduction in an inappropriate context could exacerbate inflammation. Indeed, IL-22 is involved in the pathogenesis of several intestinal diseases (www.ncbi.nlm.nih.gov). Elevated IL-22 has been observed in Crohn’s disease lesions, where it correlates with active inflammation; however, IL-22 also helps drive epithelial recovery, suggesting a complex, context-dependent role. Therapeutically, blocking IL-22 has been considered in psoriasis (to reduce keratinocyte overgrowth), whereas recombinant IL-22 or IL-22 fusion proteins have been explored in ulcerative colitis to enhance mucosal healing – highlighting the dual nature of IL-22 in disease.
Chronic Infections and Immune Deficiency: Because IL-22 strengthens barrier defenses, a deficiency in IL-22 can lead to increased susceptibility to infections at barrier sites. For example, patients with HIV or other immunodeficiencies often have reduced IL-22 levels, which is associated with microbial translocation from the gut and skin infections. A notable example is Hidradenitis suppurativa (also known as acne inversa), a chronic inflammatory skin disease: studies have found low IL-22 levels in these patients, and IL-22 deficiency is thought to contribute to the chronic nature of the disease lesions (pubmed.ncbi.nlm.nih.gov). In a 2012 study, HS patients had significantly reduced IL-22-producing T cells, suggesting that insufficient IL-22-mediated repair may permit ongoing inflammation and bacterial persistence in lesions (pubmed.ncbi.nlm.nih.gov). Conversely, excess IL-22 can be problematic in certain infections by fueling inflammation – for instance, in COVID-19, IL-22 is one of the cytokines elevated during the immune response to SARS-CoV-2. IL-22 levels were found to be up-regulated in patients with mild/moderate COVID-19 (pmc.ncbi.nlm.nih.gov) and are part of the complex cytokine milieu in severe cases (though IL-22’s exact role in COVID-19 pathology vs. protection is still under investigation). Given its association with tissue repair, some hypothesize IL-22 might help regenerate lung epithelium after viral injury; indeed, IL-22 is considered a crucial cytokine in host immunity against infections like COVID-19 (www.ncbi.nlm.nih.gov). Research is ongoing to determine if augmenting IL-22 could mitigate lung damage in viral pneumonia or if blocking IL-22 is beneficial in cytokine storm conditions – early data suggest IL-22’s effect in viral disease can be protective in lung tissue recovery, distinguishing it from purely pro-inflammatory cytokines.
Allergy and Asthma: IL-22 has also been linked to allergic inflammation. In diseases like atopic dermatitis (eczema) and asthma, IL-22 is produced by Th22/Th17 cells and can contribute to barrier dysfunction. In atopic dermatitis, IL-22 is highly expressed in lesions and correlates with epidermal hyperplasia and impaired differentiation (leading to a defective skin barrier). Targeting IL-22 in such conditions (e.g., with IL-22 neutralizing antibodies) is being explored to restore normal barrier function.
Cancer: IL-22’s ability to promote cell survival and proliferation ties it to cancer development in chronically inflamed tissues. IL-22 is overexpressed in several cancers, especially those arising from epithelial cells in the context of inflammation. For example, colorectal cancer arising from IBD-affected colon may be accelerated by IL-22, as IL-22 creates a proliferative, pro-survival environment for preneoplastic cells. In the liver, chronically elevated IL-22 (due to hepatitis or fatty liver inflammation) can contribute to hepatocellular carcinoma (HCC) by continually stimulating hepatocyte survival and proliferation – although IL-22 also induces acute phase reactants, the mitogenic effect on hepatocytes in a dysregulated environment may favor tumorigenesis (pmc.ncbi.nlm.nih.gov). A recent study highlighted the IL-22–IL-22BP axis in HCC: low levels of the decoy IL-22BP (meaning unopposed IL-22 signaling) were associated with tumor progression, suggesting IL-22 promotes liver tumor cell growth when not properly restrained (pubmed.ncbi.nlm.nih.gov). Additionally, IL-22 receptors are expressed on some cancer cells; for example, glioblastoma cells have been shown to express IL-22RA1 and respond to IL-22 by activating STAT3, which enhances their survival and resistance to apoptosis (www.genome.jp). This finding (from a 2015 study) indicates that tumors can co-opt the IL-22/STAT3 pathway to support malignant cell survival, linking IL-22 to cancer cell-intrinsic signaling. Other cancers where IL-22 is implicated include gastric cancer (often linked with IL-22 from tumor-infiltrating lymphocytes), lung cancer (IL-22 can be elevated in smokers and in COPD-related lung tumors), and pancreatic cancer. However, IL-22’s role can vary – in some contexts it might help tissue integrity and prevent dysplasia (as in acute colitis), whereas in established tumors it usually appears to favor tumor growth or immune evasion (through tissue repair mechanisms that also shield tumor cells).
Ophthalmologic and Other Conditions: Gene association studies have linked IL22 to conditions like scleritis (inflammatory disease of the eye sclera) (www.genecards.org), where IL-22 may contribute to the local immune response and tissue damage. IL22 gene polymorphisms have been examined in diseases such as type 1 diabetes, systemic lupus erythematosus, and atherosclerosis, although findings are not always consistent. In summary, IL-22 is broadly involved in diseases characterized by epithelial barrier disruption and chronic inflammation, and it can be either pathogenic or protective depending on the context. Its unique dual nature makes it an attractive yet challenging target for therapeutic intervention.
IL-22 is highly conserved across vertebrate species, reflecting its fundamental role in immune defense of barrier tissues. Genes orthologous to human IL22 have been identified in mammals, birds, and even lower vertebrates such as amphibians and fish (pubmed.ncbi.nlm.nih.gov). In fact, teleost fish possess an IL-22 homolog and the requisite IL-22 receptor components (IL-22RA1, IL-10R2) and an IL-22BP, indicating that the IL-22 signaling system was already in place early in vertebrate evolution (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). The IL-22 protein sequence is moderately conserved – for example, human IL-22 shares roughly ~70–80% amino acid identity with mouse IL-22, and key cysteine residues and functional motifs are preserved. This conservation extends to structure: the 3D structure of zebrafish IL-22 has been solved and is highly similar to that of human IL-22, displaying the same 6-helix bundle fold and disulfide bond pattern (pubmed.ncbi.nlm.nih.gov). Such structural conservation despite sequence divergence (teleost IL-22 diverges in sequence but retains the fold) underscores the strong evolutionary pressure to maintain IL-22’s function. Phylogenetic analysis suggests that IL-22 (and the closely related IL-26) arose early in the evolution of the IL-10 family cytokine cluster (pubmed.ncbi.nlm.nih.gov). IL-22 and IL-26 likely split off as a distinct branch after IL-10, meaning the ability to signal to epithelial cells via IL-22RA1 is an ancient adaptation in the immune system. No IL-22 homologs are found in invertebrates (since the class II cytokine family is vertebrate-specific), emphasizing that IL-22’s emergence aligns with the development of adaptive immunity and sophisticated barrier defense mechanisms in vertebrates. Even among mammals, IL-22’s sequence is quite conserved – human IL-22 can cross-react with some other species’ receptors (e.g., human IL-22 is active on mouse cells that express the IL-22 receptor, albeit with different affinity), which is why in vivo mouse models using human IL-22 or vice versa have been partially successful. This cross-species activity further illustrates conserved receptor-ligand interactions. Overall, the IL22 gene exemplifies how important barrier immunity cytokines have been preserved through evolution to protect organisms against environmental microbes while maintaining tissue homeostasis.
Discovery of IL-22 (2000): IL-22 was first identified around 2000 by two independent groups. Dumoutier et al. cloned a novel IL-10-related gene induced in T cells, originally named IL-TIF (IL-10-related T-cell Inducible Factor) (www.genome.jp). They showed IL-TIF/IL-22 could act on hepatoma cells to induce acute phase proteins, suggesting a role in liver inflammation and the acute phase response (www.genome.jp). Around the same time, Xie et al. reported a novel cytokine (which turned out to be the same IL-22) that signals through components of the class II cytokine receptor family (www.genome.jp). This study demonstrated that IL-22 utilizes the IL-22R1 (at that time called “CRF2-9”) and IL-10R2 (“CRF2-4”) receptor subunits, distinct from IL-10 which uses IL-10R1/IL-10R2 (www.genome.jp). These early findings established IL-22 as a member of the IL-10 family with unique target-cell specificity (hepatocytes, epithelial cells) and receptor usage.
Structure-function analyses: Several structural biology studies have been pivotal in understanding IL-22. In 2005, Xu et al. solved the crystal structure of IL-22 at 2.6 Å resolution, revealing the six α-helix bundle monomer and confirming the two disulfide bonds and glycosylation sites (www.genome.jp). Later, in 2008, Jones et al. solved the co-crystal structure of IL-22 bound to its high-affinity receptor IL-22RA1 (www.genome.jp). This provided insight into the IL-22/receptor interface, mapping key binding residues on IL-22 and showing how IL-22RA1 engages one face of the IL-22 molecule while IL-10R2 would bind another region. Interestingly, these studies noted IL-22 remains monomeric in solution (unlike IL-10 which is a tight dimer) (pmc.ncbi.nlm.nih.gov), explaining why IL-22 functions independently. The structural data also explained the necessity of IL-22’s N-linked glycans for receptor binding – one study observed that glycosylation (particularly at Asn54 in helix A) can affect IL-22’s affinity for IL-22R1 (pmc.ncbi.nlm.nih.gov). These foundational structure-function works guide current efforts to engineer IL-22 mutants or design blocking antibodies (like those that prevent IL-22 from binding IL-22RA1).
Role in inflammatory disease models: Numerous animal model studies have elucidated IL-22’s functions:
IL-22 in lung and viral infections: Recent studies (2020–2022) have examined IL-22 in influenza and COVID-19 models. For instance, therapeutic IL-22 has shown promise in preclinical models of influenza-induced lung injury, helping to regenerate airway epithelium. In the context of COVID-19, some researchers have proposed using IL-22 or IL-22 agonists to rebuild lung tissue post-infection (pmc.ncbi.nlm.nih.gov) (based on IL-22’s known role in lung epithelial repair). These avenues are still in experimental stages, but they underscore the translational interest in IL-22.
Clinical correlations: Elevated IL-22 levels have been observed in patients with diseases like psoriasis, atopic dermatitis, rheumatoid arthritis, IBD, COPD, and even cancer (e.g. IL-22 is found in the tumor microenvironment of colon and liver cancers) (www.genecards.org) (www.genome.jp). Clinical trials are underway targeting the IL-22 pathway: for example, an IL-22 neutralizing antibody (fezakinumab) was tested in atopic dermatitis and showed some improvement in skin lesions. Conversely, an IL-22 agonist (F-652, a recombinant IL-22 dimer) has been tested in alcoholic hepatitis to promote liver regeneration with some positive signals. These studies are informed by the foundational research outlined above and could pave the way for IL-22–targeted therapies in inflammatory diseases.
In conclusion, IL-22 is a multifaceted cytokine with crucial roles in mucosal immunity, inflammation, and tissue homeostasis. Its gene and protein have been well-characterized in terms of sequence, structure, and function, providing a solid basis for Gene Ontology annotation. IL-22 exhibits cytokine activity and interleukin-22 receptor binding functions (www.genecards.org), operates in the extracellular region after secretion (www.proteinatlas.org), and participates in key biological processes such as inflammatory response, innate immune response, defense response to bacteria, epithelial cell proliferation, and tissue regeneration (www.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The rich literature spanning from molecular structure to animal models and human disease associations makes IL-22 an important gene for curated annotation in the context of immune and epithelial biology.