Alt. symbols: IL1F7 | FIL1 | FIL1Z | FIL1(ZETA) | IL-1H4 | IL-1RP1 | IL-1F7

Approved name: interleukin 37
Alt. names: interleukin 1 family, member 7 (zeta) | interleukin 1, zeta, interleukin-1 homolog 4, interleukin-1-related protein

Location: 2q14.1: 112911165 - 112918882 (+)
Gene type: protein_coding, 5 transcripts.

Scores: LoFtool: | pLI: 0.00783606 | LOEUF: 1.729

HGNC: 15563

NCBI: 27178, RefSeq: NG_029219.1

Ensembl: ENSG00000125571.10

LRG_ | Status: none

OMIM: 605510

Expression | ProteinAtlas

IL37 encodes IL-37, an antiinflammatory IL-1 family cytokine, that acts as a suppressor of innate inflammatory and immune responses. It can signal intracellularly through caspase-1-dependent activation and nuclear translocation with SMAD3 or extracellularly after secretion and binding to IL18Ralpha and IL1R8 (PMID: 34248996). IL-37 suppresses, or reduces, pro-inflammatory cytokine production, including IL-1alpha, IL-1beta, and IL-6, but spares anti-inflammatory cytokines (PMID: 25327443). IL-37 can also bind to IL-18BP, leading the two cytokines to potentially reduce each other's anti-inflammatory effects (PMID: 34248996). Though 5 isoforms are known, not all may be biologically active; the beta isoform contains the greatest number of exons (PMID: 25327443).

Biallelic mutations in IL37, encoding IL-37, an antiinflammatory IL-1 family cytokine, have also been linked to infantile onset IBD (ulcerative colitis) [OMIM: 619398]. IL-37 is predominantly expressed by macrophages or dendritic cells and can suppress TNF, IL-1beta, and IL-6 signaling either intracellularly through nuclear translocation with SMAD3 or extracellularly after secretion and binding to an IL-1R8 and IL-18R1 heterodimeric receptor complex highly expressed in the GI tract. Zhang et al. (2021) identified a homozygous LOF missense mutation in IL37 in a 2-year-old boy born to consanguineous Turkish parents who presented at 4 months of age with recurrent bloody diarrhea, FTT, anemia, leukocytosis, and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (PMID: 33674380). Immunophenotyping showed normal proportions of monocytes, CD4+, and CD8+ T cells and a large proportion of undifferentiated naïve T and B cells, but primary patient monocyte-derived dendritic cells (moDCs) appeared to produce more TNF and IFN-gamma relative to healthy controls. Of note, unlike VEO-IBD patients with IL10 pathway mutations who are often treatment-refractory and may need hematopoietic stem cell transplants, this patient’s IBD appeared to be well-controlled by standard immunosuppressive agents. [Load More]