Interleukin 35
Interleukin 35 (IL-35) is a recently discovered anti-inflammatory 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.[1] IL-35 can block the development of Th1 and Th17 cells by limiting early T cell proliferation.[2]
Structure
IL-35 and its receptor
IL-35 is a dimeric protein composed of IL-12α and IL-27β chains, which are encoded by two separate genes called IL12A and EBI3 (Epstein-Barr virus-induced gene 3), respectively.[3][4] IL-35 receptor consists of IL-12Rβ2 (part of the IL-12R) and gp130 (part of IL-27R) 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.[5] On regulatory B-cells, IL-35 signals through the IL-12Rβ2 and IL-27Rα subunits.[6]
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[7]
Function
Expression
Secreted by regulatory T-cells (
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
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 factor HNF4α.[19]
Tumor
Given its suppressive function, IL-35 is also involved in tumor progression and tumor immune surveillance.[20] Elevated circulating IL-35 levels have been found in several human tumors such as acute myeloid leukemia,[21] pancreatic ductal adenocarcinoma[22] and colorectal cancer.[23]
Moreover, Forkhead box protein 3 (
References
- PMID 27020866.
- ^ S2CID 4425281.
- PMID 28648331.
- S2CID 19146526.
- PMID 22306691.
- PMID 24743305.
- PMID 8551575.
- ^ PMID 24572363.
- PMID 23152566.
- PMID 29371247.
- PMID 22438968.
- S2CID 38306559.
- PMID 26922678.
- PMID 28850026.
- PMID 22814351.
- PMID 25796985.
- PMID 26224624.
- S2CID 207367998.
- PMID 29561254.
- PMID 25919641.
- PMID 22783403.
- PMID 24121041.
- PMID 24040445.
- S2CID 226218796.