Gene Symbol: Il1rap
Description: interleukin 1 receptor accessory protein
Alias: 6430709H04Rik, AI255955, AV239853, IL-1RAcP, interleukin-1 receptor accessory protein, IL-1 receptor accessory protein, interleukin-33 receptot beta chain
Species: mouse
Products:     Il1rap

Top Publications

  1. Ali S, Huber M, Kollewe C, Bischoff S, Falk W, Martin M. IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells. Proc Natl Acad Sci U S A. 2007;104:18660-5 pubmed
    ..Furthermore, they suggest that IL-1RAcP is used by more than one alpha-chain of the IL-1 receptor family and thus may resemble a common beta-chain of that family. ..
  2. Cullinan E, Kwee L, Nunes P, Shuster D, Ju G, McIntyre K, et al. IL-1 receptor accessory protein is an essential component of the IL-1 receptor. J Immunol. 1998;161:5614-20 pubmed
    ..Finally, IL-1R AcP is an essential signal transducing component of the functional IL-1R and should represent a novel target for blocking IL-1 function in human disease. ..
  3. Smith D, Lipsky B, Russell C, Ketchem R, Kirchner J, Hensley K, et al. A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1. Immunity. 2009;30:817-31 pubmed publisher
    ..These findings implicate AcPb as an additional component of the highly regulated IL-1 system and suggest that it may play a role in modulating CNS responses to IL-1 and the interplay between inflammation and neuronal survival. ..
  4. Greenfeder S, Nunes P, Kwee L, Labow M, Chizzonite R, Ju G. Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J Biol Chem. 1995;270:13757-65 pubmed
    ..Therefore, the functional IL-1 receptor appears to be a complex composed of at least two subunits. ..
  5. Yoon D, Dinarello C. Differential effects of anti-IL-1R accessory protein antibodies on IL-1alpha or IL-1beta-induced production of PGE(2) and IL-6 from 3T3-L1 cells. J Biochem Mol Biol. 2007;40:562-70 pubmed
    ..Our data suggest that domain III of IL-1RAcP may be involved in the formation or stabilization of the IL-1RI/IL-1 complex by binding to epitopes on domain III of the IL-1RI created following IL-1 binding to the IL-1RI. ..
  6. Gosselin D, Bellavance M, Rivest S. IL-1RAcPb signaling regulates adaptive mechanisms in neurons that promote their long-term survival following excitotoxic insults. Front Cell Neurosci. 2013;7:9 pubmed publisher
    ..These data suggest that in a context of excitotoxicity, stimulation of IL-1RAcPb signaling may promote the activity of a key neuroprotective mechanism. ..
  7. Blumberg H, Dinh H, Trueblood E, Pretorius J, Kugler D, Weng N, et al. Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J Exp Med. 2007;204:2603-14 pubmed
    ..In summary, dysregulated expression of novel agonistic and antagonistic IL-1 family member ligands can promote cutaneous inflammation, revealing potential novel targets for the treatment of inflammatory skin disorders. ..
  8. Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, et al. Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat Cell Biol. 2000;2:346-51 pubmed
    ..As overexpression of Tollip results in impaired NF-kappaB activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway. ..
  9. Yamagata A, Yoshida T, Sato Y, Goto Ito S, Uemura T, Maeda A, et al. Mechanisms of splicing-dependent trans-synaptic adhesion by PTPδ-IL1RAPL1/IL-1RAcP for synaptic differentiation. Nat Commun. 2015;6:6926 pubmed publisher
    ..Our results thus reveal the decoding mechanism of splice-insert signaling codes for synaptic differentiation induced by trans-synaptic adhesion between PTPδ and IL1RAPL1/IL-1RAcP. ..

More Information


  1. Liu C, Chalmers D, Maki R, De Souza E. Rat homolog of mouse interleukin-1 receptor accessory protein: cloning, localization and modulation studies. J Neuroimmunol. 1996;66:41-8 pubmed
    ..On the other hand, the presence of the IL-1RAcP in brain areas which show an absence of type I IL-1 receptors suggests additional functions for this protein in the rat. ..
  2. Hand N, Horner A, Master Z, Boateng L, Leguen C, Uvaydova M, et al. MicroRNA profiling identifies miR-29 as a regulator of disease-associated pathways in experimental biliary atresia. J Pediatr Gastroenterol Nutr. 2012;54:186-92 pubmed publisher
    ..set of hepatic genes regulated by miR-29 and identified 2 mRNA targets of potential pathological relevance in experimental BA, Igf1 and Il1RAP. We have used reporter assays to confirm that Igf1 and Il1RAP are direct targets of miR-29.
  3. Laye S, Liège S, Li K, Moze E, Neveu P. Physiological significance of the interleukin 1 receptor accessory protein. Neuroimmunomodulation. 2001;9:225-30 pubmed
    b>Interleukin 1 receptor accessory protein (IL-1RAcP) is an essential signal-transducing component of the IL-1 receptor type I. The recent availability of IL-1RAcP-deficient (KO) mice allows to study the in vivo function of IL-1RAcP...
  4. Lockett A, Goebl M, Harrington M. Transient membrane recruitment of IRAK-1 in response to LPS and IL-1beta requires TNF R1. Am J Physiol Cell Physiol. 2008;295:C313-23 pubmed publisher
    ..In the absence of TNF R1-dependent events, exposure to LPS or IL-1 leads to hyperactivation of the inflammatory response. ..
  5. Huang H, Chen H, Evankovich J, Yan W, Rosborough B, Nace G, et al. Histones activate the NLRP3 inflammasome in Kupffer cells during sterile inflammatory liver injury. J Immunol. 2013;191:2665-79 pubmed publisher
    ..These novel findings illustrate a new mechanism by which extracellular histones and activation of NLRP3 inflammasome contribute to liver damage and the activation of innate immunity during sterile inflammation. ..
  6. Radons J, Gabler S, Wesche H, Korherr C, Hofmeister R, Falk W. Identification of essential regions in the cytoplasmic tail of interleukin-1 receptor accessory protein critical for interleukin-1 signaling. J Biol Chem. 2002;277:16456-63 pubmed
    ..Taken together, our data indicate that box 3 of IL-1RAcP is critical for IL-1-dependent NF-kappaB activation and stabilization of IL-2 mRNA via JNK, whereas aa 527-534 largely contribute to IL-2 promoter activation. ..
  7. Jensen L, Muzio M, Mantovani A, Whitehead A. IL-1 signaling cascade in liver cells and the involvement of a soluble form of the IL-1 receptor accessory protein. J Immunol. 2000;164:5277-86 pubmed
    ..This suggests that sIL-1RAcP may act as an inhibitor of IL-1 by directly interacting with IL-1RI to abolish its capacity to transduce signal. ..
  8. Palmer G, Lipsky B, Smithgall M, Meininger D, Siu S, Talabot Ayer D, et al. The IL-1 receptor accessory protein (AcP) is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33. Cytokine. 2008;42:358-64 pubmed publisher
    ..These observations identify AcP as a shared co-receptor within the IL-1 family that is essential for IL-33 signaling and suggest a novel role for sAcP in modulating the activity of IL-33. ..
  9. Radons J, Dove S, Neumann D, Altmann R, Botzki A, Martin M, et al. The interleukin 1 (IL-1) receptor accessory protein Toll/IL-1 receptor domain: analysis of putative interaction sites in vitro mutagenesis and molecular modeling. J Biol Chem. 2003;278:49145-53 pubmed
  10. Wesche H, Neumann D, Resch K, Martin M. Co-expression of mRNA for type I and type II interleukin-1 receptors and the IL-1 receptor accessory protein correlates to IL-1 responsiveness. FEBS Lett. 1996;391:104-8 pubmed
    ..These results suggest that the expression of the IL-1RAcP correlates with IL-1 responsiveness and they point to a pivotal role for the IL-1RAcP in IL-1 signal generation. ..
  11. Yoshida T, Shiroshima T, Lee S, Yasumura M, Uemura T, Chen X, et al. Interleukin-1 receptor accessory protein organizes neuronal synaptogenesis as a cell adhesion molecule. J Neurosci. 2012;32:2588-600 pubmed publisher
    ..Thus, IL-1RAcP represents an interesting molecular link between immune systems and synapse formation in the brain. ..
  12. Brikos C, Wait R, Begum S, O Neill L, Saklatvala J. Mass spectrometric analysis of the endogenous type I interleukin-1 (IL-1) receptor signaling complex formed after IL-1 binding identifies IL-1RAcP, MyD88, and IRAK-4 as the stable components. Mol Cell Proteomics. 2007;6:1551-9 pubmed
    ..The only component of the IL-1RI signaling complex that dissociated is IRAK-1. Our study is therefore the first detailed description of the endogenous IL-1RI complex. ..
  13. Chackerian A, Oldham E, Murphy E, Schmitz J, Pflanz S, Kastelein R. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex. J Immunol. 2007;179:2551-5 pubmed
    ..The implications of this shared usage of IL-1RAcP by IL-1(alpha and beta) and IL-33 are discussed. ..
  14. Thomas H, Irawaty W, Darwiche R, Brodnicki T, Santamaria P, Allison J, et al. IL-1 receptor deficiency slows progression to diabetes in the NOD mouse. Diabetes. 2004;53:113-21 pubmed
    ..3 TCR transgenic NOD mice but prolonged the time to diabetes in BDC2.5 TCR transgenic NOD mice. We conclude that IL-1R deficiency slows progression to diabetes in NOD mice but on its own does not prevent diabetes. ..
  15. Andre R, Moggs J, Kimber I, Rothwell N, Pinteaux E. Gene regulation by IL-1beta independent of IL-1R1 in the mouse brain. Glia. 2006;53:477-83 pubmed
    ..These results show that IL-1beta exclusively downregulates alpha-syntrophin expression independently of IL-1R1, and suggest the expression of additional functional IL-1 receptors in the CNS. ..
  16. Liang Y, Seymour R, Sundberg J. Inhibition of NF-?B signaling retards eosinophilic dermatitis in SHARPIN-deficient mice. J Invest Dermatol. 2011;131:141-9 pubmed publisher
    ..Compound-null mutants for both the IL1 receptor accessory protein (Il1rap(tm1Roml)) and SHARPIN (Sharpin(cpdm)) resulted in mice having decreased skin disease severity...
  17. Boch J, Yoshida Y, Koyama Y, Wara aswapati N, Peng H, Unlu S, et al. Characterization of a cascade of protein interactions initiated at the IL-1 receptor. Biochem Biophys Res Commun. 2003;303:525-31 pubmed
    ..A model is presented that reflects the specific molecular interactions responsible for recruiting signaling intermediates to the IL-1 receptor cytoplasmic domains. ..
  18. Orelio C, Haak E, Peeters M, Dzierzak E. Interleukin-1-mediated hematopoietic cell regulation in the aorta-gonad-mesonephros region of the mouse embryo. Blood. 2008;112:4895-904 pubmed publisher
    ..Our results suggest that IL-1 is an important homeostatic regulator at the earliest time of HSC development, acting to limit the differentiation of some HSCs along the myeloid lineage...
  19. Rankin A, Mumm J, Murphy E, Turner S, Yu N, McClanahan T, et al. IL-33 induces IL-13-dependent cutaneous fibrosis. J Immunol. 2010;184:1526-35 pubmed publisher
    ..Collectively, our results identify IL-33 as a previously unrecognized profibrotic mediator in skin and highlight the cellular and molecular pathways by which this pathology develops. ..
  20. Parnet P, Garka K, Bonnert T, Dower S, Sims J. IL-1Rrp is a novel receptor-like molecule similar to the type I interleukin-1 receptor and its homologues T1/ST2 and IL-1R AcP. J Biol Chem. 1996;271:3967-70 pubmed
  21. Davis C, Dunbrasky D, Oonk M, Taishi P, Opp M, Krueger J. The neuron-specific interleukin-1 receptor accessory protein is required for homeostatic sleep and sleep responses to influenza viral challenge in mice. Brain Behav Immun. 2015;47:35-43 pubmed publisher
    ..Body temperature and locomotor activity responses after viral challenge were lower and mortality was higher in AcPbKO than in WT mice. We conclude that neuron-specific AcPb plays a critical role in host defenses and sleep homeostasis. ..
  22. Wolf G, Yirmiya R, Goshen I, Iverfeldt K, Holmlund L, Takeda K, et al. Impairment of interleukin-1 (IL-1) signaling reduces basal pain sensitivity in mice: genetic, pharmacological and developmental aspects. Pain. 2003;104:471-80 pubmed
    ..These findings suggest that basal pain sensitivity is genetically, developmentally and tonically influenced by IL-1 signaling. ..
  23. Agerstam H, Hansen N, von Palffy S, Sandén C, Reckzeh K, Karlsson C, et al. IL1RAP antibodies block IL-1-induced expansion of candidate CML stem cells and mediate cell killing in xenograft models. Blood. 2016;128:2683-2693 pubmed
    ..Interleukin-1 receptor accessory protein (IL1RAP; IL1R3) is a coreceptor of interleukin-1 receptor type 1 and has been found upregulated on CML stem cells...