Details for: IL1RL2

Gene ID: 8808

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: IL1RL2

Ensembl ID: ENSG00000115598

Description: interleukin 1 receptor like 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • conjunctival epithelial cell CL1000432
    CSI 2.3
    rCSI 3.51%
    PRS 95.35
  • basal cell of epidermis CL0002187
    CSI 1.53
    rCSI 2.71%
    PRS 74.46
  • suprabasal keratinocyte CL4033013
    CSI 1.22
    rCSI 1.99%
    PRS 75
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.92
    rCSI 3.48%
    PRS 89.64
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.82
    rCSI 2.95%
    PRS 88.26

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [IL1RL2](/details-gene/8808) (Interleukin 1 Receptor Like 2) is a protein-coding gene located on chromosome 2q12.1 that encodes a member of the interleukin-1 (IL-1) receptor family. As a cell surface receptor, [IL1RL2](/details-gene/8808) is an integral component of the innate immune system, primarily involved in mediating inflammatory responses. Initial studies identified it as an orphan receptor, but it is now recognized as the signaling receptor for IL-36 cytokines ([Link](https://doi.org/10.4049/jimmunol.167.3.1440)). Expression data indicates its most significant role is in epithelial barrier tissues, with the highest significance observed in [conjunctival epithelial cell](/details-cell/CL1000432), [basal cell of epidermis](/details-cell/CL0002187), and [suprabasal keratinocyte](/details-cell/CL4033013), suggesting a crucial function in orchestrating immune and defense responses at mucosal and cutaneous surfaces. ## Cellular Roles and Expression Landscape The expression profile of [IL1RL2](/details-gene/8808) strongly points to a specialized function in epithelial cells that form the body's primary barriers against the environment. **Overall**, the gene shows the highest significance in [conjunctival epithelial cell](/details-cell/CL1000432) (CSI: 2.30), highlighting a potential role in ocular surface immunity and inflammation. This is followed by high significance in key cells of the skin, including [basal cell of epidermis](/details-cell/CL0002187) (CSI: 1.53) and [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 1.22). This pattern suggests that [IL1RL2](/details-gene/8808) is a key sensor and transducer of inflammatory signals within the epidermis. Interestingly, the data also reveals a notable, albeit lower, significance in specific neuronal populations, including [near-projecting glutamatergic cortical neuron](/details-cell/CL4023012) (CSI: 0.92) and [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041) (CSI: 0.82). This suggests a less characterized role for [IL1RL2](/details-gene/8808) in the central nervous system, possibly related to neuro-immune crosstalk or responses to inflammatory stimuli within the brain. The gene's concentrated expression in these distinct epithelial and neuronal cell types indicates a highly specialized function rather than a ubiquitous housekeeping role. ## Pathways and Molecular Function Functionally, [IL1RL2](/details-gene/8808) is annotated as a transmembrane receptor with [interleukin-1 receptor activity](/details-go/GO:0004908), located on the [cell surface](/details-go/GO:0009986) and [plasma membrane](/details-go/GO:0005886). Its primary role is to participate in the [cell surface receptor signaling pathway](/details-go/GO:0007166), which initiates downstream cellular responses upon ligand binding. The biological processes associated with [IL1RL2](/details-gene/8808) are overwhelmingly related to host defense and inflammation. It is a key player in the [innate immune response](/details-go/GO:0045087), the [inflammatory response](/details-go/GO:0006954), and the broader [cellular defense response](/details-go/GO:0006968). Its involvement is further specified in Reactome pathways, including [Cytokine signaling in immune system](/details-reactome/R-HSA-1280215) and, more specifically, [Interleukin-1 family signaling](/details-reactome/R-HSA-446652). The most critical pathway it participates in is the [Interleukin-36 pathway](/details-reactome/R-HSA-9014826). Research has shown that IL-36 cytokines stimulate synovial fibroblasts and chondrocytes to produce inflammatory mediators via [IL1RL2](/details-gene/8808) ([Link](https://doi.org/10.1186/ar1946)) and promote myeloid cell activity in the skin ([Link](https://doi.org/10.4049/jimmunol.1301481)). This function is consistent with its high expression in keratinocytes, which are major producers and responders to IL-36 in skin inflammation. ## Research Directions The specific expression of [IL1RL2](/details-gene/8808) in barrier tissues and its central role in the IL-36 signaling axis, which is implicated in several inflammatory diseases, suggest several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in [conjunctival epithelial cell](/details-cell/CL1000432), [IL1RL2](/details-gene/8808) signaling is a critical driver of ocular surface inflammation in conditions like allergic conjunctivitis or dry eye disease, where it mediates the pro-inflammatory effects of IL-36 released by stressed epithelial cells. 2. The high expression of [IL1RL2](/details-gene/8808) in [basal cell of epidermis](/details-cell/CL0002187) and its role in the IL-36 pathway suggest that aberrant [IL1RL2](/details-gene/8808) activation in these progenitor keratinocytes is a key event in the pathogenesis of psoriasis, contributing to the characteristic epidermal hyperproliferation and inflammatory feedback loop. 3. The unexpected expression in cortical glutamatergic neurons suggests a role in neuroinflammation. It is hypothesized that [IL1RL2](/details-gene/8808) on these neurons acts as a sensor for brain-derived IL-36, modulating neuronal excitability or survival in response to brain injury or neurodegenerative disease. **Key Experimental Approach:** To test the hypothesis regarding the role of [IL1RL2](/details-gene/8808) in psoriasis (Hypothesis 2), a robust experimental plan could be implemented. A conditional knockout mouse model could be generated to specifically delete *Il1rl2* in keratinocytes (e.g., using a KRT14-Cre driver). These mice and their wild-type littermates would be subjected to an imiquimod-induced model of psoriasis. The resulting skin phenotype would be quantitatively assessed through measurements of ear thickness, histological analysis of epidermal acanthosis, and flow cytometric quantification of infiltrating immune cells (e.g., neutrophils, Th17 cells). In parallel, primary keratinocytes isolated from both genotypes would be stimulated *in vitro* with recombinant IL-36, and downstream signaling (e.g., NF-kappaB and MAPK phosphorylation) and gene expression of inflammatory cytokines (e.g., *Il6*, *Cxcl1*) would be measured by western blot and qPCR, respectively. A significant reduction in psoriatic features in the knockout mice would confirm the critical role of [IL1RL2](/details-gene/8808) in keratinocyte-mediated skin inflammation. **Therapeutic Potential:** [IL1RL2](/details-gene/8808) represents a highly promising therapeutic target for a range of inflammatory diseases, particularly those affecting the skin like psoriasis. As a cell surface receptor that initiates a pro-inflammatory cascade, **inhibition** is the clear therapeutic strategy. Its specific expression pattern on epithelial cells at sites of inflammation suggests that targeting it could offer a localized anti-inflammatory effect with potentially fewer systemic side effects than broader immunosuppressants. Therapeutic modalities could include monoclonal antibodies designed to block the binding of IL-36 ligands to [IL1RL2](/details-gene/8808) or small molecule inhibitors that disrupt its intracellular signaling domain. Such approaches are actively being explored for treating pustular psoriasis and other autoinflammatory conditions.

Genular Protein ID: 3138063521

Symbol: ILRL2_HUMAN

Name: Interleukin-1 receptor-like 2

UniProtKB Accession Codes:

Q9HB29 A4FU63 Q13525 Q45H74 Q53TU8 Q587I8

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 5 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EC 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 12 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRINTS 3 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 2 RefSeq 2 Rhea 2 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10882729

Title: Identification and characterization of two members of a novel class of the interleukin-1 receptor (IL-1R) family. Delineation of a new class of IL-1R-related proteins based on signaling.

PubMed ID: 10882729

DOI: 10.1074/jbc.m004077200

PubMed ID: 8898719

Title: Cloning of a cDNA encoding a novel interleukin-1 receptor related protein (IL1R-rp2).

PubMed ID: 8898719

DOI: 10.1016/s0165-5728(96)00047-1

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11466363

Title: Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2.

PubMed ID: 11466363

DOI: 10.4049/jimmunol.167.3.1440

PubMed ID: 16646978

Title: The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes.

PubMed ID: 16646978

DOI: 10.1186/ar1946

PubMed ID: 24829417

Title: IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin.

PubMed ID: 24829417

DOI: 10.4049/jimmunol.1301481

Sequence Information:

  • Length: 575
  • Mass: 65405
  • Checksum: 7AC0FCAB43A2A6CD
  • Sequence:
    • MWSLLLCGLS IALPLSVTAD GCKDIFMKNE ILSASQPFAF NCTFPPITSG EVSVTWYKNS 
SKIPVSKIIQ SRIHQDETWI LFLPMEWGDS GVYQCVIKGR DSCHRIHVNL TVFEKHWCDT 
SIGGLPNLSD EYKQILHLGK DDSLTCHLHF PKSCVLGPIK WYKDCNEIKG ERFTVLETRL 
LVSNVSAEDR GNYACQAILT HSGKQYEVLN GITVSITERA GYGGSVPKII YPKNHSIEVQ 
LGTTLIVDCN VTDTKDNTNL RCWRVNNTLV DDYYDESKRI REGVETHVSF REHNLYTVNI 
TFLEVKMEDY GLPFMCHAGV STAYIILQLP APDFRAYLIG GLIALVAVAV SVVYIYNIFK 
IDIVLWYRSA FHSTETIVDG KLYDAYVLYP KPHKESQRHA VDALVLNILP EVLERQCGYK 
LFIFGRDEFP GQAVANVIDE NVKLCRRLIV IVVPESLGFG LLKNLSEEQI AVYSALIQDG 
MKVILIELEK IEDYTVMPES IQYIKQKHGA IRWHGDFTEQ SQCMKTKFWK TVRYHMPPRR 
CRPFPPVQLL QHTPCYRTAG PELGSRRKKC TLTTG