Ask about this productRelated genes to: IL33 protein
- Gene:
- IL1RL1 NIH gene
- Name:
- interleukin 1 receptor like 1
- Previous symbol:
- -
- Synonyms:
- ST2, FIT-1, ST2L, ST2V, DER4, T1, IL33R
- Chromosome:
- 2q12.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-17
- Date modifiied:
- 2017-07-07
- Gene:
- IL33 NIH gene
- Name:
- interleukin 33
- Previous symbol:
- C9orf26
- Synonyms:
- DVS27, DKFZp586H0523, NF-HEV, IL1F11
- Chromosome:
- 9p24.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-18
- Date modifiied:
- 2014-11-19
Related products to: IL33 protein
Related articles to: IL33 protein
- Spinal cord injury (SCI) triggers a complex and evolving cascade of pathological events in which neuroinflammation and microenvironmental imbalance critically constrain repair. Among the cellular mediators, microglia exhibit remarkable functional plasticity, transitioning across diverse states that can either support tissue repair or exacerbate secondary damage. However, the mechanisms governing this dynamic reprogramming remain incompletely understood, limiting the development of effective immunomodulatory strategies. Recent evidence identifies the interleukin-33 (IL-33)/ST2 axis as an emerging, context-dependent regulator linking immune responses to neural repair. Rapidly released as an alarmin following injury, IL-33 modulates microglial function across spatiotemporal dimensions. Here, we propose a two-stage working model integrating direct evidence from SCI with extrapolated insights from broader central nervous system (CNS) pathologies. While acute IL-33 signaling is directly demonstrated in SCI models to limit early neuroinflammation and contain tissue damage, its putative role in driving a subsequent reparative microglial phenotype-encompassing metabolic adaptation and specialized phagocytic clearance-remains a hypothesis largely inferred from brain injury and neurodegenerative paradigms. Furthermore, we explore how IL-33 might modulate intercellular crosstalk with regulatory T cells and astrocytes, emphasizing that these downstream reparative mechanisms require definitive validation within the specific microenvironment of the injured spinal cord. In this Review, we synthesize current advances in the understanding of SCI pathology, microglial heterogeneity, and IL-33-mediated signaling. We highlight how IL-33 integrates inflammatory, metabolic, and transcriptional programs to drive microglial functional reprogramming, and we evaluate emerging therapeutic strategies targeting this pathway. Despite promising preclinical findings, challenges remain in optimizing delivery, timing, and safety. A deeper understanding of the IL-33/ST2 axis and its context-dependent effects may enable precise immunomodulation, offering new avenues to overcome barriers to regeneration and improve functional recovery after SCI. - Source: PubMed
Publication date: 2026/09/16
Ma ZiyuLu ZichengZhou ZipengWang TianhaoZhang JinhuiMa YifeiNiu RuihanZhang LichengDeng JunhaoZhao Yongfei - pneumonia triggers a complex, dynamic host response, yet the cellular coordination of inflammation and repair remains poorly defined. - Source: PubMed
Publication date: 2026/09/08
Zong FuliangWang YanHu LingfeiLi LuZhou DongshengZhao JinYang Huiying - The dynamic interplay between pro- and anti-inflammatory cytokines plays a crucial role in regulating host immune responses. In our earlier study, we showed that Leishmania donovani-induced IL-33 destabilizes host cytokine dynamics by downregulating TNF-α and IL-12 and ensures intramacrophage parasite survival. Another pertinent host favorable proinflammatory cytokine is Il-1β, maturation of which depends on the activation of NLRP3 inflammasome complex. Our present study highlights that independent neutralization of IL-33 and its receptor ST2, resulted in elevated levels of NLRP3 both at messenger RNA and protein levels, along with increased levels of mature IL-1β. Reduced NLRP3 expression during infection was correlated with decreased protein levels of p65, the major subunit of NF-κB transcription factor complex. An unaltered transcript level of p65 in infected macrophages along with reduced protein expression suggested that post-translational modification and ubiquitination-mediated p65 degradation in the presence of IL-33 was found to be driven by the ubiquitin ligase SOCS1. Administration of IL-33-neutralizing antibody in infected mice resulted in enhanced expression of both p65 and NLRP3, along with increased production of TNF-α, IL-12, and IL-1β, suggesting that IL-33 regulates these cytokines through a shared intermediary, p65. Neutralizing IL-33 during infection led to a reduction in SOCS1 expression, and SOCS1 knockdown by targeted short hairpin RNA in infected mice restores p65 levels, reactivates NLRP3 expressions, and reduces parasite burden in the visceral organs. This study highlights the IL-33/SOCS1 pathway as a potential target for host-directed therapeutic strategies aimed at restoring protective immunity during chronic leishmaniasis. - Source: PubMed
Roy SouraviMandal MayumiBanerjee MadhurimaMadbhagat PratibhaChande AjitUkil Anindita - Soluble suppression of tumorigenicity 2 (sST2), a decoy receptor of interleukin-33 (IL-33), is involved in allergic inflammation and may serve as a biomarker in allergic rhinitis (AR). MicroRNA-223 (miR-223) has also been implicated in allergic inflammation. To investigate serum sST2 and miR-223 as potential biomarkers of disease activity and treatment-associated changes in patients with house dust mite (HDM)-induced moderate-to-severe allergic rhinitis (MSAR) undergoing sublingual immunotherapy (SLIT). This study included 54 patients with moderate-to-severe AR (MSAR) and 54 healthy controls (HC). Serum sST2, total IgE, HDM-specific IgE, and eosinophil counts were measured. Serum miR-223 relative expression was assessed using real-time PCR. Clinical severity was assessed using the total nasal symptom score (TNSS) and visual analogue scale (VAS). MSAR patients received SLIT for 6 months. Treatment response was defined as a ≥ 30% reduction in TNSS from baseline. Serum sST2 and miR-223 were significantly higher in MSAR patients than in healthy controls (p < 0.001). sST2 correlated positively with HDM-specific IgE and eosinophil counts and decreased significantly after six months of treatment (p < 0.001). Post-treatment sST2 was lower in responders, whereas baseline sST2 did not differ significantly between groups. ROC analysis showed good discrimination of MSAR from HC for sST2 (AUC = 0.933) and miR-223 (AUC ≈ 0.96). Serum sST2 and miR-223 show promising potential as candidate biomarkers of HDM-induced MSAR. The decrease in sST2 after treatment suggests its potential value for monitoring treatment-associated changes. Further studies are needed to validate these findings.Trial registration Retrospectively registered on ClinicalTrials.gov, registered at 25/2/ 2026, Identifier (NCT07436208). Registered at: https://clinicaltrials.gov/study/NCT07436208. - Source: PubMed
Publication date: 2026/09/08
Mokhtar Ghada AGebriel Manar GAbdelnour Hanim MSalah Abd El Azeem El Sayed MohamedHadhoud Ahmed NagyRoman Sylvia WMohamed Noura MostafaElGwad Asmaa Mohamed AbdIbraheem Ahmed A ANofal Hanaa AOmran Farida HMohammed Shrouk A - IL-33, an alarmin cytokine binding to IL1RL1 (ST2) receptor, plays a multifaceted role in cancer. Using an HPV16-E7 oncoprotein-mediated murine model of squamous intraepithelial hyperplasia, a pre-stage of squamous cell carcinoma (SCC), we characterised the interactions of hyperproliferative epithelial cells and immune cells regulated by IL-33 and IL1RL1. We show that basal epithelial cells in epithelial hyperplasia co-express IL-33 and genes involved in MHC class II antigen presentation and in epithelial stress response. Using spatial transcriptomics, we demonstrate that IL1RL1Foxp3Tregs are in close proximity to IL-33-expressing cells, in both the murine model and in human cervical intraepithelial neoplastic tissues. Cytoplasmic location of IL-33 is associated with its bioactivity, and we show that a subset of epithelial cells in epithelial hyperplasia contains high levels of cytoplasmic IL-33. Genetic deletion of the IL1RL1 gene led to partial rejection of HPV16-E7-expressing skin grafts, demonstrating that IL1RL1 plays a functional role in mediating immune suppression in epithelial hyperplasia. IL1RL1-deletion further led to a significant reduction in Tregs in epithelial hyperplasia. The IL1RL1 signalling pathway, therefore, represents a potential therapeutic target for intraepithelial hyperplasia and SCC. - Source: PubMed
Publication date: 2026/09/01
Zhou ChenhaoGonzalez Cruz JazminaTeoh Siok MinTran MinhGoh DeniseNarayanan DivyaaTan XiaoDang Thi Viet TrinhTuong Zewen KelvinGillinder KevinBashaw AbateWells James WFrazer Ian HNguyen QuanChen YuYu MeihuaChandra Janin