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
- Interleukin-33 (IL-33) and soluble ST2 (sST2) are critical regulators of tissue-derived inflammation, and their dysregulation is usually implicated in various inflammatory disorders. Despite this, how these circulating proteins behave over time in healthy individuals remains poorly defined. Therefore, defining reference concentrations in healthy cohorts is important for interpreting disease-associated changes attributed to these proteins. - Source: PubMed
Publication date: 2026/08/13
Anabe DeniseTeräsjärvi Johanna TBarkoff Alex-MikaelMertsola JussiHe Qiushui - Interleukin-33 (IL-33) is a central regulator of immune responses and inflammation, and genetic variation in IL33 and its receptor IL1RL1 (ST2) is strongly linked to disease susceptibility, notably asthma. Emerging evidence suggests that IL-33 also influences hematopoietic processes and platelet biology, indicating functions beyond canonical immunity. We investigated two missense variants identified in a patient with unexplained thrombocytopenia: a rare novel IL33 variant, c.385T>C (p.Tyr129His) and the common IL1RL1 variant c.1501_1502CA>AG (p.Gln501Arg), previously associated with reduced IL-33 signaling. Structural modeling revealed that IL-33 Y129H disrupts a conserved hydrogen bond within the IL-33/ST2/IL-1RAcP ternary complex, destabilizing receptor engagement. Functional assays confirmed markedly reduced binding affinity and biological activity, establishing Y129H as a loss-of-function variant. The IL1RL1 Q501R variant affects the Toll/IL-1 receptor (TIR) domain, critical for recruiting adapter proteins such as MyD88. Modeling revealed pronounced perturbation in a peripheral helix of the TIR domain, potentially impacting adapter recruitment and downstream signaling, providing a mechanistic basis for its protective association with asthma. Together, these findings provide structural and functional insights into clinically relevant IL33 and IL1RL1 variants. Their simultaneous occurrence in a patient with thrombocytopenia further supports a potential role for this pathway in platelet homeostasis and stress-responsive hematopoiesis. - Source: PubMed
Publication date: 2026/08/04
Gelon LucieRoga StéphaneNahoum VirginiePasquet MarlènePrade NaïsDufrechou StéphanieLargeaud LaetitiaDelabesse EricVoisin SophieGirard Jean-PhilippeMourey LionelLefrançais Emma - Alzheimer's disease (AD) is a multifactorial disorder involving various pathological mechanisms, such as amyloidosis, immune dysfunctions, and synaptic impairments, which are important therapeutic targets. Repurposing drugs to target these mechanisms offers a promising approach to reduce the costs and duration of drug development. Genetic studies underscore the critical role of microglial clearance of amyloid-beta (Aβ) in AD pathogenesis. Specifically, soluble ST2 (sST2)-one of the two major isoforms of the ST2 protein encoded by the IL1RL1 (interleukin-1 receptor-like 1) gene-acts as a decoy receptor isoform that interferes with IL-33/ST2 signaling and has been identified as a disease-modifying factor that impairs microglial Aβ clearance functions. In this study, we investigated drug repurposing opportunities to modulate sST2 levels and alleviate AD pathologies. Unbiased screening of commonly used medications in AD patients, followed by validation in model systems, identified trazodone-an antidepressant used to treat major depressive disorder-as a leading negative regulator of sST2. Trazodone primarily suppresses sST2 expression through its antagonistic effects on adrenergic signaling. In the APP/PS1 transgenic mouse model of AD, trazodone treatment enhanced microglial interaction with Aβ and alleviated Aβ pathology. Furthermore, trazodone reduced neurodegeneration and rescued synaptic deficits in APP/PS1 mice. Comprehensive molecular profiling of APP/PS1 mouse brains showed that trazodone restored the expression of synaptic proteins critical for synaptic integrity and plasticity. Overall, these findings demonstrate that trazodone is a promising repurposing candidate for AD that targets underlying immune dysfunctions and synaptic impairment. - Source: PubMed
Publication date: 2026/07/14
Wong Daniel Y KFu Wing-YuUhm HyebinJiang YuanbingYip Yuki C CMok Vincent C TKwok Timothy C YOuyang LiFu Amy K YIp Nancy Y - Aspirin-exacerbated respiratory disease (AERD) is a distinct asthma endotype marked by asthma, nasal polyposis, and respiratory reactions to COX-1 inhibitors. Early and accurate identification of AERD remains clinically challenging. - Source: PubMed
Publication date: 2026/06/02
Modena Brian DBagci Mehmet FurkanHoyte FlaviaMoore MarkZahid SoombalHill JenniferBarberis NicoleDo ToanCanty EthanSpierling Bagsic Samantha ROzturk YusufWhite Andrew - Chagas disease, caused by Trypanosoma cruzi, is characterized by a complex interplay between parasite persistence and host-driven immunopathology. Although the IL-33/ST2 axis is known to regulate type 2 immunity and tissue repair, its contribution to tissue homeostasis during chronic infection remains poorly understood. Using ST2-deficient (ST2) and wild-type BALB/c mice followed for up to 100 days postinfection, we investigated the role of IL-33/ST2 signaling in coordinating hepato-intestinal response and systemic immunity. ST2 deficiency induced coordinated systemic disturbances, including platelet expansion and hyperalbuminemia. At the tissue level, loss of ST2 exacerbated hepatic inflammation and fibrotic remodeling. In the colon, ST2 mice displayed increased nitric oxide production and enhanced parasite clearance, but developed marked structural alterations. Our findings suggest that IL-33/ST2 signaling is associated with regulatory programs. ST2 deficiency was associated with a reduction in patrolling monocytes, suggesting impaired homeostatic endothelial monitoring. This profile also coincided with inflammatory monocyte-derived dendritic cell differentiation and lowered macrophage regulatory activity. This altered profile was associated with amplified IL-12-driven Th1 and cytotoxic T-cell responses while impairing IL-10-associated regulatory niches, resulting in multiorgan inflammation. These findings suggest that IL-33/ST2 signaling may contribute to immunoregulatory balance during T. cruzi infection and identify this axis as a candidate pathway for future mechanistic and therapeutic investigation. - Source: PubMed
Cardozo Marcelo EduardoCirilo Tatyane Martinsda Rocha Rihs José BryanSouza Jorge Lucas Nascimentode Brito Duval IsabelaAntunes-Porto Ana Rafaelado Amaral Luisa Vitor BragaOliveira Fernando Bento RodriguesRicci Mayra Fernandade Oliveira Santos Laura LisSantana Lívia Fernanda DiasSilva Luiza PinheiroAmorim Chiara Cássia OliveiraLemos Gabriela Gomes MonteiroJunior Getulío Mota E Silvada Silva Oliveira IzabelaDos Reys Marina Possade Oliveira Ana Laura GrossiCassali Geovanni DantasMagalhães Luisa Mourão DiasBueno Lilian LacerdaMachado Fabiana SimãoFujiwara Ricardo Toshio