Interleukin 1 receptor (type1)

The interleukin-1 receptor (type 1) is a cytokine receptor that belongs to the interleukin-1 receptor family. The coding gene IL1R1 is located on the gene loci 2q11.2-q12.1.

The interleukin-1 receptor is an important mediator involved in many cytokine-induced immune and inflammatory responses. Upon binding to its ligand, the cytokine interleukin-1 , the protein complex associates with the coreceptor IL1RAP to form the high-affinity interleukin-1 receptor complex, which mediates interleukin-1-dependent activation of NF-kappaB, MAPK and other signaling pathways. The signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88 and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits.

The receptor protein also binds ligands with comparable affinity. For example, binding of the interleukin-1 receptor antagonist(IL-1RA) prevents binding with the coreceptor IL-1RAP to form the active signaling complex. Involved in interleukin-1beta-mediated costimulation of IFNgamma production by Th1 cells (Tominaga K et al. 2000)

Diseases associated with mutations of the interleukin-1 receptor protein include:

• Chronic recurrent multifocal osteomyelitis 3 (CRI3)

and

• Schnitzler syndrome, a rare, late-onset, non-hereditary (familial) autoinflammatory disease (AID). According to the Strasbourg diagnostic criteria established in 2012 (see below), Schnitzler's syndrome shows a chronic urticarial rash and a monoclonal gammopathy of the IgM and, less frequently, IgG type (85%/15% of cases; mandatory main criteria/de Koning HD 2014). The minor Strasbourg criteria of the disease include recurrent fever, abnormal bone remodeling with or without bone pain, a neutrophilic infiltrate in the skin biopsy and leukocytosis or elevated CRP.

1. Chen S. (2022) et al.Rare mutations in NLRP3 and NLRP12 associated with familial cold autoinflammatory syndrome: two Chinese pedigrees.Clin Rheumatol 41: 3461-3470
2. Cozzi A et al. (2016) Cutaneous manifestations of adult-onset Still's disease: a case report and review of literature. Clin Rheumatol 35: 1377-1382.
3. de Koning HD (2014) Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy 4: 41
4. Elling E et al. (2008) Schnitzler's syndrome: chronic urticaria and monoclonal gammopathy-an autoinflammatory syndrome. JDDG 6: 626-631
5. Mosley B et al. (1987) The interleukin-1 receptor binds the human interleukin-1 alpha precursor but not the interleukin-1 beta precursor. J Biol Chem 262:2941-294
6. Tominaga K et al. (2000) IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells. Int Immunol 12:151-160.