Interleukin 35 is a recently discovered anti-infl ammatory cytokine from the IL-12 family. Member of IL-12 family - IL-35 is produced by wide range of regulatory lymphocytes and plays a role in immune suppression. IL-35 can block the development of Th1 and Th17 cells by limiting early T cellproliferation.
Structure
IL-35 and its receptor
IL-35 is a dimeric proteincomposed ofIL-12α and IL-27β chains, which are encoded by two separate genes called IL12A and EBI3, respectively. IL-35 receptor consists of IL-12Rβ2 and gp130 chains. Compared to these two related interleukins, IL-35 is also able to signal through only one of the aforementioned chains. This was proven in vivo when absence of either of the receptor chains did not influence effects of IL-35. EBI3 is a homologue to IL-12 p40 and to the ciliary neurotrophic factor receptor, whose expression is induced in B lymphoblastoid cells by EBV infection
Function
Expression
Secreted by regulatory T-cells, regulatory B-cells or even CD8+ regulatory T cells, IL-35 suppresses inflammatory responses of immune cells. IL-35 is not constitutively expressed in tissues, but the gene encoding IL-35 is transcribed by vascular endothelial cells, smooth muscle cells and monocytes after activation with proinflammatory stimuli. IL-35 has selective activities on different T-cell subsets; it induces proliferation of Treg cell populations but reduces activity of Th17 cell populations.
Role in disease
Autoimmune conditions
Studies in mice show the absence of either IL-35 chain from regulatory Tregs reduces the cells' ability to suppress inflammation. This has been observed during cell culture experiments and using an experimental model for inflammatory bowel disease. A group of scientists established a CIA mouse model to show suppressive effects of IL-35. Intraperitoneal injection of IL-35 in the tested subjects lowered expression of several factors linked to this disease. The effect of IL-35 in this case seems to be the inhibition of STAT1 signalling pathway. Another experiment performed on a mouse model of EAE has shown, that mice lacking IL-35-producing B cells are unable to recover from the T-cell mediated demyelination but are resistant to infection by pathogenic intracellular microbe Salmonella typhimurium.
Infectious diseases
It has been shown that IL-35 increases replication of HBV virus both in vitro and in transgenic mice by targeting its transcription factorHNF4α.
