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Gene Review

IL1RL1  -  interleukin 1 receptor-like 1

Homo sapiens

Synonyms: DER4, FIT-1, IL33R, Interleukin-1 receptor-like 1, Protein ST2, ...
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Disease relevance of IL1RL1

  • We also established stable transfectants of a human glioblastoma cell line, T98G, that express human ST2L constitutively, and we confirmed cell-surface expression of human ST2L protein on the transfectants [1].
  • This study investigated whether the prevalence of hay fever in RA is low and if severity of RA (T1 cell activity) can be influenced by the concomitant occurrence of a T2 cell mediated disease (hay fever) [2].
  • A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapy [3].
  • Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma [4].
  • PATIENTS AND INTERVENTIONS: Whole blood from 14 consecutive patients undergoing AAAR withdrawn prior to surgery (T1), at the end of ischemia (T2), 90 min after declamping (T3) and on the first postoperative day (T4) was cultured in the absence or presence of LPS [5].

Psychiatry related information on IL1RL1

  • In contrast, within the CG, paternal parenting stress was negatively associated with adaptive parenting at T1 but showed no enduring negative effects in longitudinal analyses [6].
  • For both groups, there was a direct positive association between T1 use utility and T2 alcohol consumption and an indirect association with T2 alcohol problems via alcohol consumption [7].
  • Consistent with the proposal that children's self-perceptions become more realistic with age, Time 1 (T1) teacher ratings were more highly correlated with student self-ratings at T2 than T1 and contributed to the prediction of T2 self-concept beyond effects mediated by T1 self-concepts [8].

High impact information on IL1RL1

  • In addition several new mediators of control have emerged, including IL-18, the intriguing Th2-selective T1/ST2 product, and heterogeneity in dendritic cells capable of directing cytokine-independent Th development [9].
  • Hybridization with the 9q34.3 probe detected multiple transcripts in SUP-T1 RNA and small amounts of larger transcripts in T cells lacking the t(7;9)(q34;q34.3) translocation [10].
  • Sequence analysis of DNA from the t(7;9)(q34;q34.3) translocation of SUP-T1 revealed that chromosome 9 DNA had recombined with DNA 5' to rearranged D-J regions in the beta T cell receptor gene of chromosome 7 [10].
  • DNA containing breakpoints of two different t(7;9) chromosomal translocations was cloned from the T lymphoblastic tumor cell lines SUP-T1 and SUP-T3 [10].
  • The cytokine IL-33 is the specific ligand for ST2 [11].

Chemical compound and disease context of IL1RL1


Biological context of IL1RL1

  • The human ST2 gene (IL1RL1) contains 13 exons and spans 40 kb in length [1].
  • Here, we have investigated T1/ST2 signal transduction, using either transient overexpression of T1/ST2 or a cross-linking monoclonal antibody to activate cells [17].
  • The ST2 gene encodes both membrane-bound ST2L and soluble ST2 (sST2) proteins by alternative splicing [18].
  • To analyze the cis-regulatory elements responsible for the induced transcription, we fused a 1.6-kilobase segment of the rat T1 kininogen promoter to a reporter gene, chloramphenicol acetyltransferase (CAT) [19].
  • These data indicate that the sequence homology between IL-1RI and T1/ST2 indicates a functional homology as well [20].

Anatomical context of IL1RL1

  • Here we analyze the mechanisms and therapeutic implications of the unique ability of ST2 to promote development and function of type 2 helper T cells through a positive feedback loop, as well as to act as a negative feedback modulator of macrophage pro-inflammatory function [21].
  • The former group includes the receptor for the important Th1 cytokine IL-18, and T1/ST2, which may have a role in Th2 cell function [22].
  • Similarly, in Balb/c-3T3 cells, the expression of soluble ST2 mRNA and protein was induced by pro-inflammatory stimuli such as TNF, IL-1alpha, IL-1beta and PMA in both exponentially growing and quiescent cells [23].
  • The labeled human ST2 protein bound with myeloma-derived RPMI8226 cells among the various B-cell lines, indicating possible involvement of ST2 in T-cell/B-cell interaction [24].
  • Using the RT-PCR method, we found that the ST2 gene was broadly expressed in hematopoietic cell lines [24].

Associations of IL1RL1 with chemical compounds

  • In vitro exposure to LPS augmented expression of IL-1RI, T1/ST2 and MyD88, whereas it inhibited that of IL-1RII and rsc786 [25].
  • On the other hand, one of the Th2 cell lines, D10, expressed ST2L (transmembrane form) without stimulation, while co-stimulation by PMA and A23187 induced ST2 (soluble form) mRNA [24].
  • Deletion analyses revealed two regions important for tissue-specific and induced regulation of T1 kininogen: sequences proximal to base pair -73 conferred enhanced expression in liver-derived cells and a distal region that conferred responsiveness to conditioned medium, recombinant IL-6, and dexamethasone [19].
  • Transfection of ST2V cDNA into COS7 cells in the presence of [(35)S] methionine and cysteine produced radiolabeled 40 kDa protein, which is recognized by specific monoclonal antibody against human ST2 [26].
  • We describe in this report the cloning and characterisation of a cDNA encoding a homologue of ST2L in Atlantic salmon (Salmo salar) [27].

Physical interactions of IL1RL1


Regulatory relationships of IL1RL1

  • ST2 suppresses IL-6 production via the inhibition of IkappaB degradation induced by the LPS signal in THP-1 cells [28].

Other interactions of IL1RL1

  • T1/ST2--an IL-1 receptor-like modulator of immune responses [21].
  • CONCLUSION: These results argue in favour of the exploration of treatments aimed at regulation of a possible imbalance in T1/T2 cell activity in RA [2].
  • Pharmacokinetic analysis following the intravenous bolus injection has shown that IL-4 is rapidly cleared (mean T1/2 = 19 +/- 8.7 min) from a small compartment (mean Vd = 4.9 +/- 3.68 l) probably indicating that IL-4 is retained in the systemic circulation or at most the extracellular fluid volume [29].
  • These results demonstrated that ST2 negatively regulates LPS-induced IL-6 production via the inhibition of IkappaB degradation in THP-1 cells [28].
  • Investigating GATA-3 gene regulation in human T cells we have found that naive T cells highly express GATA-3, and during early T2 or T1 polarization, respectively, they either maintain or quickly down-regulate expression [30].

Analytical, diagnostic and therapeutic context of IL1RL1


  1. The cloning and nucleotide sequence of human ST2L cDNA. Li, H., Tago, K., Io, K., Kuroiwa, K., Arai, T., Iwahana, H., Tominaga, S., Yanagisawa, K. Genomics (2000) [Pubmed]
  2. Mutual antagonism of rheumatoid arthritis and hay fever; a role for type 1/type 2 T cell balance. Verhoef, C.M., van Roon, J.A., Vianen, M.E., Bruijnzeel-Koomen, C.A., Lafeber, F.P., Bijlsma, J.W. Ann. Rheum. Dis. (1998) [Pubmed]
  3. A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapy. Price, P., Keane, N.M., Lee, S., Lim, A.F., McKinnon, E.J., French, M.A. Immunology (2006) [Pubmed]
  4. Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma. Brunner, M., Krenn, C., Roth, G., Moser, B., Dworschak, M., Jensen-Jarolim, E., Spittler, A., Sautner, T., Bonaros, N., Wolner, E., Boltz-Nitulescu, G., Ankersmit, H.J. Intensive care medicine. (2004) [Pubmed]
  5. Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair. Ziegenfuss, T., Wanner, G.A., Grass, C., Bauer, I., Schüder, G., Kleinschmidt, S., Menger, M.D., Bauer, M. Intensive care medicine. (1999) [Pubmed]
  6. Predictors of Parenting Behavior Trajectories Among Families of Young Adolescents with and without Spina Bifida. Greenley, R.N., Holmbeck, G.N., Rose, B.M. Journal of pediatric psychology (2006) [Pubmed]
  7. An affective and cognitive model of marijuana and alcohol problems. Simons, J.S., Carey, K.B. Addictive behaviors. (2006) [Pubmed]
  8. Structure, stability, and development of young children's self-concepts: a multicohort-multioccasion study. Marsh, H.W., Craven, R., Debus, R. Child development. (1998) [Pubmed]
  9. Signaling and transcription in T helper development. Murphy, K.M., Ouyang, W., Farrar, J.D., Yang, J., Ranganath, S., Asnagli, H., Afkarian, M., Murphy, T.L. Annu. Rev. Immunol. (2000) [Pubmed]
  10. Analysis of DNA surrounding the breakpoints of chromosomal translocations involving the beta T cell receptor gene in human lymphoblastic neoplasms. Reynolds, T.C., Smith, S.D., Sklar, J. Cell (1987) [Pubmed]
  11. An IL-1 family member requires caspase-1 processing and signals through the ST2 receptor. Dinarello, C.A. Immunity (2005) [Pubmed]
  12. Importance of urinary interleukin-18 in intravesical immunotherapy with bacillus calmette-guérin for superficial bladder tumors. Eto, M., Koga, H., Noma, H., Yamaguchi, A., Yoshikai, Y., Naito, S. Urologia internationalis. (2005) [Pubmed]
  13. Combined analysis of polymorphisms of the tumor necrosis factor-alpha and interleukin-10 promoter regions and polymorphic xenobiotic metabolizing enzymes in psoriasis. Reich, K., Westphal, G., Schulz, T., Müller, M., Zipprich, S., Fuchs, T., Hallier, E., Neumann, C. J. Invest. Dermatol. (1999) [Pubmed]
  14. Is true FISP imaging reliable in the evaluation of venous thrombosis? Pedrosa, I., Morrin, M., Oleaga, L., Baptista, J., Rofsky, N.M. AJR. American journal of roentgenology. (2005) [Pubmed]
  15. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Weinberg, E.O., Shimpo, M., De Keulenaer, G.W., MacGillivray, C., Tominaga, S., Solomon, S.D., Rouleau, J.L., Lee, R.T. Circulation (2002) [Pubmed]
  16. Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction. Shimpo, M., Morrow, D.A., Weinberg, E.O., Sabatine, M.S., Murphy, S.A., Antman, E.M., Lee, R.T. Circulation (2004) [Pubmed]
  17. Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction. Brint, E.K., Fitzgerald, K.A., Smith, P., Coyle, A.J., Gutierrez-Ramos, J.C., Fallon, P.G., O'Neill, L.A. J. Biol. Chem. (2002) [Pubmed]
  18. Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. Shimizu, M., Matsuda, A., Yanagisawa, K., Hirota, T., Akahoshi, M., Inomata, N., Ebe, K., Tanaka, K., Sugiura, H., Nakashima, K., Tamari, M., Takahashi, N., Obara, K., Enomoto, T., Okayama, Y., Gao, P.S., Huang, S.K., Tominaga, S., Ikezawa, Z., Shirakawa, T. Hum. Mol. Genet. (2005) [Pubmed]
  19. Interleukin-6 responsiveness and cell-specific expression of the rat kininogen gene. Chen, H.M., Considine, K.B., Liao, W.S. J. Biol. Chem. (1991) [Pubmed]
  20. T1/ST2 signaling establishes it as a member of an expanding interleukin-1 receptor family. Mitcham, J.L., Parnet, P., Bonnert, T.P., Garka, K.E., Gerhart, M.J., Slack, J.L., Gayle, M.A., Dower, S.K., Sims, J.E. J. Biol. Chem. (1996) [Pubmed]
  21. T1/ST2--an IL-1 receptor-like modulator of immune responses. Trajkovic, V., Sweet, M.J., Xu, D. Cytokine Growth Factor Rev. (2004) [Pubmed]
  22. The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products. Bowie, A., O'Neill, L.A. J. Leukoc. Biol. (2000) [Pubmed]
  23. Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli. Kumar, S., Tzimas, M.N., Griswold, D.E., Young, P.R. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  24. The expression of ST2 gene in helper T cells and the binding of ST2 protein to myeloma-derived RPMI8226 cells. Yanagisawa, K., Naito, Y., Kuroiwa, K., Arai, T., Furukawa, Y., Tomizuka, H., Miura, Y., Kasahara, T., Tetsuka, T., Tominaga, S. J. Biochem. (1997) [Pubmed]
  25. Divergent effects of LPS on expression of IL-1 receptor family members in mononuclear phagocytes in vitro and in vivo. Saccani, S., Polentarutti, N., Penton-Rol, G., Sims, J.E., Mantovani, A. Cytokine (1998) [Pubmed]
  26. Tissue distribution and subcellular localization of a variant form of the human ST2 gene product, ST2V. Tago, K., Noda, T., Hayakawa, M., Iwahana, H., Yanagisawa, K., Yashiro, T., Tominaga , S. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  27. Cloning and characterisation of a putative ST2L homologue from Atlantic salmon (Salmo salar). Stansberg, C., Subramaniam, S., Olsen, L., Secombes, C.J., Cunningham, C. Fish Shellfish Immunol. (2003) [Pubmed]
  28. ST2 suppresses IL-6 production via the inhibition of IkappaB degradation induced by the LPS signal in THP-1 cells. Takezako, N., Hayakawa, M., Hayakawa, H., Aoki, S., Yanagisawa, K., Endo, H., Tominaga, S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  29. Recombinant human interleukin-4 (rhu IL-4) administered by the intravenous and subcutaneous routes in patients with advanced cancer--a phase I toxicity study and pharmacokinetic analysis. Prendiville, J., Thatcher, N., Lind, M., McIntosh, R., Ghosh, A., Stern, P., Crowther, D. Eur. J. Cancer (1993) [Pubmed]
  30. Kinetics of GATA-3 gene expression in early polarizing and committed human T cells. Lantelme, E., Mantovani, S., Palermo, B., Campanelli, R., Sallusto, F., Giachino, C. Immunology (2001) [Pubmed]
  31. Construction of ELISA system to quantify human ST2 protein in sera of patients. Kuroiwa, K., Li, H., Tago, K., Iwahana, H., Yanagisawa, K., Komatsu, N., Oshikawa, K., Sugiyama, Y., Arai, T., Tominaga, S.I. Hybridoma (2000) [Pubmed]
  32. Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Weinberg, E.O., Shimpo, M., Hurwitz, S., Tominaga, S., Rouleau, J.L., Lee, R.T. Circulation (2003) [Pubmed]
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