IL37
Function
Immune regulatory cytokine that acts as a suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. Signaling can occur via two mechanisms, intracellularly through nuclear translocation with SMAD3 and extracellularly after secretion and binding to its receptor composed of IL18R1 and IL18RAP. Suppresses, or reduces, pro-inflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation.
Involvement in disease
Inflammatory bowel disease 31, autosomal recessive
IBD31
A form of inflammatory bowel disease, a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology and a multifactorial inheritance pattern. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. IBD31 patients suffer from infantile ulcerative colitis and present with recurrent bloody diarrhea with anemia and leukocytosis, extensive lymphoplasmocytic infiltration, cryptitis, and apoptotic crypt abcesses throughout the colon and rectum.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Proteolytically converted to the mature form by CASP1.
Sequence Similarities
Belongs to the IL-1 family.
Tissue Specificity
In general, low constitutive expression, if any, in healthy tissues; high expression in inflammatory counterparts, including in synovial tissues from individuals with active rheumatoid arthritis. Isoform A, isoform B and isoform C are expressed in testis, colon, placenta, lung and lymph node. Isoform D and isoform E were found only in testis and bone marrow. Whereas only isoform A is found in brain, only isoform B in kidney and only isoform C in heart.
Cellular localization
- Cytoplasm
- Cytosol
- Nucleus
- Secreted
- Stimulation with IL1B leads to colocalization with SMAD3 mostly in perinuclear regions (PubMed:20935647, PubMed:33674380). Only the CASP1-cleaved mature form translocates into the nucleus upon LPS stimulation (PubMed:18390730). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (PubMed:32272059, PubMed:33674380).
Alternative names
FIL1Z, IL1F7, IL1H4, IL1RP1, IL37, Interleukin-37, IL-37, FIL1 zeta, IL-1X, Interleukin-1 family member 7, Interleukin-1 homolog 4, Interleukin-1 zeta, Interleukin-1-related protein, IL-1F7, IL-1H, IL-1H4, IL-1 zeta, IL-1RP1