The decoy receptor interleukin 1 receptor 2 (IL-1R2), also known as CD121b, has different forms: membrane-bound (mIL-1R2), soluble secreted (ssIL-1R2), shedded (shIL-1R2), intracellular domain (IL-1R2ICD). The different forms of IL-1R2 exert not exactly similar functions. IL-1R2 can not only participate in the regulation of inflammatory response by competing with IL-1R1 to bind IL-1 and IL-1RAP, but also regulate IL-1 maturation and cell activation, promote cell survival, participate in IL-1-dependent internalization, and even have biological activity as a transcriptional cofactor. In this review, we provide a detailed description of the biological characteristics of IL-1R2 and discuss the expression and unique role of IL-1R2 in different immune cells. Importantly, we summarize the role of IL-1R2 in immune regulation from different autoimmune diseases, hoping to provide a new direction for in-depth studies of pathogenesis and therapeutic targets in autoimmune diseases.

The interleukin 1 (IL-1) family plays a significant role in the innate immune response. IL-1 receptor 2 (IL-1R2) is the decoy receptor of IL-1. It is a negative regulator that can be subdivided into membrane-bound and soluble types. IL-1R2 plays a role in the IL-1 family mainly through the following mechanisms: formation of inactive signaling complexes upon binding to the receptor auxiliary protein and inhibition of ligand IL-1 maturation. This review covers the roles of IL-1R2 in kidney disorders. Chronic kidney disease, acute kidney injury, lupus nephritis, IgA nephropathy, renal clear cell carcinoma, rhabdoid tumor of kidney, kidney transplantation, and kidney infection were all shown to have abnormal IL-1R2 expression. IL-1R2 may be a potential marker and a promising therapeutic target for kidney disease.

Inappropriate immune activity is key in the pathogenesis of multiple diseases, and it is typically driven by excess inflammation and/or autoimmunity. IL-1 is often the effector owing to its powerful role in both innate and adaptive immunity, and, thus, it is tightly controlled at multiple levels. IL-1R2 antagonizes IL-1, but effects of losing this regulation are unknown. We found that IL-1R2 resolves inflammation by rapidly scavenging free IL-1. Specific IL-1R2 loss in germinal center (GC) T follicular regulatory (Tfr) cells increased the GC response after a first, but not booster, immunization, with an increase in T follicular helper (Tfh) cells, GC B cells, and antigen-specific antibodies, which was reversed upon IL-1 blockade. However, IL-1 signaling is not obligate for GC reactions, as WT and Il1r1-/- mice showed equivalent phenotypes, suggesting that GC IL-1 is normally restrained by IL-1R2. Fascinatingly, germline Il1r2-/- mice did not show this phenotype, but conditional Il1r2 deletion in adulthood recapitulated it, implying that compensation during development counteracts IL-1R2 loss. Finally, patients with ulcerative colitis or Crohn\'s disease had lower serum IL-1R2. All together, we show that IL-1R2 controls important aspects of innate and adaptive immunity and that IL-1R2 level may contribute to human disease propensity and/or progression.

Retinopathy of prematurity (ROP) is the leading cause of blindness in children, but there is no safe and effective treatment available. Interleukin-1 receptor type 2 (IL1R2) acts as a decoy receptor for IL-1 may affect ROP progression. This study aimed to investigate the role of IL1R2 in ROP. A microglial cell model was established under hypoxia conditions and co-cultured with choroidal endothelial cells, while an oxygen-induced retinopathy (OIR) model was also established. Microglial activation and IL1R2 levels in retinal tissues were analyzed using immunofluorescence assay. Endothelial cell migration was evaluated by Transwell assay and scratch test, angiogenesis was assessed using ELISA and tube formation assay, and proliferation was evaluated by EdU assay. The HIF1α/PFKFB3 pathway was analyzed by western blot. We observed that IL1R2 expression was predicted to be upregulated in ROP and was increased in hypoxia-treated BV2 cells. Additionally, IL1R2 levels were upregulated in the retinal tissues of OIR mice and correlated with microglial activation. In vitro experiments, we found that hypoxia promoted endothelial cell migration, angiogenesis, proliferation, and activated the HIF1α/PFKFB3 pathway, which were rescued by IL1R2 knockdown. Moreover, NHWD-870 (a HIF1α/PFKFB3 pathway inhibitor) suppressed endothelial cell migration, angiogenesis, and proliferation induced by IL1R2 overexpression. In conclusion, IL1R2 facilitates the migration, angiogenesis, and proliferation of choroidal endothelial cells by activating the HIF1α/PFKFB3 pathway to regulate ROP progression.

This study aimed to investigate whether interleukin 1β (IL-1β) and soluble IL-1 receptor 2 (sIL-1R2) are expressed in human granulosa cells (GCs) and relate to ovarian steroidogenesis. Ninety-six women undergoing in vitro fertilization (IVF) were recruited. RT-PCR and immunocytochemistry were used to detect mRNAs and proteins of IL-1β and IL-1R2, respectively. The steroidogenesis of primary cultured GCs was evaluated following treatment with either IL-1β alone or IL-1β and FSH in combination. There were positive correlations between serum IL-1β and serum progesterone (r = 0.220, p = 0.032) and follicular fluid (FF) estradiol (r = 0.242, p = 0.018). Additionally, serum and FF sIL-1R2 were negatively and positively correlated with FF estradiol (r = -0.376, p = 0.005) and FF progesterone (r = 0.434, p = 0.001), respectively. The mRNA and protein expression of IL-1β and IL-1R2 became evident in GCs. IL-1β alone significantly increased estradiol secretion from GCs, but in the presence of FSH, it could notably promote progesterone secretion in addition to estradiol. In conclusion, IL-1β and sIL-1R2 are expressed in human GCs and substantially contribute to ovarian steroidogenesis, suggesting that the IL-1β system may be a potential target for optimizing ovarian hyperstimulation and steroidogenesis in IVF cycles.

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The aim of this study is to figure out the role of IL1R2 in LUAD (lung adenocarcinoma).
IL1R2, a special member of IL-1 receptor family, binds to IL-1 and plays an important role in inhibiting IL-1 pathway, which seems to be involved in tumorigenesis. Emerging studies demonstrated higher IL1R2 expression levels in several malignancies.
In the present study, we assessed the expression of IL1R2 in LUAD tissues with immunohistochemistry and explored various databases to determine whether it could be a potential prognostic biomarker and therapeutic target.
The expression level of IL1R2 in lung adenocarcinoma was analyzed by Immunohistochemistry and UALCAN database. The correlation between IL1R2 expression and the patient prognosis was identified by Kaplan-Meier plotter. The correlation of IL1R2 expression with immune infiltrates was clarified by TIMER database. The protein-protein interaction network and gene functional enrichment analysis were constructed and performed by STRING and Metascape database.
Immunohistochemistry showed that the expression of IL1R2 was higher in tumor tissues of LUAD patients and that patients with lower IL1R2 level have a better prognosis than their counterparts. We validated our findings in several online databases and found that IL1R2 gene was also positively correlated with B cells and neutrophils and biomarkers of CD8+T cells and exhausted T cells. PPI network and gene enrichment analyses showed that expression of IL1R2 was also associated with complex functionspecific networks involving IL-1 signal, NF-KappaB transcription factors.
According to these findings, we demonstrated that IL1R2 was involved in the progression and prognosis of LUAD and the underlying mechanism needs further investigation.

Guillain-Barré syndrome (GBS) is an autoimmune disorder wherein the composition and gene expression patterns of peripheral blood immune cells change significantly. It is triggered by antigens with similar epitopes to Schwann cells that stimulate a maladaptive immune response against peripheral nerves. However, an atlas for peripheral blood immune cells in patients with GBS has not yet been constructed. This is a monocentric, prospective study. We collected 5 acute inflammatory demyelinating polyneuropathy (AIDP) patients and 3 healthy controls hospitalized in the First Affiliated Hospital of Harbin Medical University from December 2020 to May 2021, 3 AIDP patients were in the peak stage and 2 were in the convalescent stage. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from these patients. Furthermore, we performed cell clustering, cell annotation, cell-cell communication, differentially expressed genes (DEGs) identification and pseudotime trajectory analysis. Our study identified a novel clonally expanded CD14+ CD163+ monocyte subtype in the peripheral blood of patients with AIDP, and it was enriched in cellular response to IL1 and chemokine signaling pathways. Furthermore, we observed increased IL1β-IL1R2 cell-cell communication between CD14+ and CD16+ monocytes. In short, by analyzing the single-cell landscape of the PBMCs in patients with AIDP we hope to widen our understanding of the composition of peripheral immune cells in patients with GBS and provide a theoretical basis for future studies.

To screen out core genes potentially prognostic for sepsis and construct a competing endogenous RNA (ceRNA) regulatory network.
Subjects included in this project were 23 sepsis patients and 10 healthy people. RNA-seq for lncRNA, miRNA and mRNA was performed in the peripheral blood samples. Differentially expressed RNAs (DER) were screened out for further analysis. GO annotation and GSEA functional clustering were performed to view the functional enrichment of DEmRNAs. Core genes of prognostic significance were screened out with the weighted correlation network analysis (WGCNA). Meta-analysis and Survival analysis was devised in different microarray datasets. RT-qPCR was conducted to validate these core genes. A ceRNA network was accordingly constructed according to the correlation analysis and molecular interaction prediction.
RNA-seq and differential analysis screened out 1,044 DEmRNAs, 66 DEmiRNAs and 155 DElncRNAs. The GO and GSEA analysis revealed that DEmRNAs are mainly involved in inflammatory response, immune regulation, neutrophil activation. WGCNA revealed 4 potential core genes, including CD247, IL-2Rβ, TGF-βR3 and IL-1R2. In vitro cellular experiment showed up-regulated expression of IL-1R2 while down-regulated of CD247, IL-2Rβ, TGF-βR3 in sepsis patients. Correspondingly, a ceRNA regulatory network was build based on the core genes, and multiple lncRNAs and miRNAs were identified to have a potential regulatory role in sepsis.
This study identified four core genes, including CD247, IL-1R2, IL-2Rβ and TGF-βR3, with potential to be novel biomarkers for the prognosis of sepsis. In the meantime, a ceRNA network was constructed aiming to guide further study on prognostic mechanism in sepsis.