Interleukin 37


Interleukin 37, also known as IL-1 family member 7, is an anti-inflammatory cytokine. Interleukines are cytokines that make an important part of immune signaling. It belongs to the interleukin-1 family. This protein is in humans encoded by the IL37 gene located on the chromosome 2.

Gene location and structure

The IL-37 gene is in the human located on the long chromosome arm of chromosome 2. There has not been found any homolog gene in mice genome. IL-37 undergoes alternative splicing with 5 different splice variants: IL-37a-e. IL-37b is the largest and most studied one, it shares the beta barrel structure that is spread within the interleukin-1 family.

Gene expression

IL-37a,b,c are being expressed in a variety of tissues - thymus, lung, colon, uterus, bone marrow. It is produced by immune cells, for example natural killer cells, activated B lymphocytes, monocytes but also by keratinocytes or epithelial cells.
Some IL-37 isoforms are tissue specific:
IL-37a - brain
IL-37b - kidney, bone marrow, blood, skin, respiratory and urogenital tract
IL-37c - heart
IL-37d - bone marrow, testis
IL-37 same as the other members of the interleukin-1 family is synthesized in a precursor form and for a full activation is a cleavage by caspase 1 needed.

Function

The mechanism of IL-37 functions is still to be elucidated. IL-37 possesses not only anti-inflmammatory effects but it is also important in antimicrobial response or antitumor immunity. The IL-37 acts intracellulary and extracellulary.

IL-37 nuclear translocation

cleaved IL-37 can translocate into cell nucleus where it forms functional complex with phosphorylated or unphosphorylated Smad3 and effects the expression of proinflammatory cytokines such as IL-1β or IFN-γ.

Interaction with IL-18 receptor

IL-37 has two similar amino acid residues with IL-18, thus can interact with IL-18 receptor. The affinity of IL-37b to IL-18R alpha subunit is much lower compared to IL-18. IL-37b interacts with IL-18 binding protein, that is an antagonist of IL-18. The binding of IL-37b enhances the IL-18BP functions.

Role in disease