Interleukin-35 translocates from the ER lumen to the extracellular region

Stable Identifier
R-HSA-448627
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
Synonyms
IL12A:EBI3(IL35) are secreted to the extracellular medium
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Interleukin-35 heterodimer is formed by interleukin-12 alpha (IL12A or IL12p35) and Interleukin 27 subunit beta (EBI3).
EBI3 monomer can be found at the endoplasmic reticulum and is not secreted since it remains associated to the protein calnexin (CANX). So is suggested EBI3 needs the association with another subunit to be released to the extracellular region (Devergne et al. 1996).
Interleukin-35 affects and is specifically produced by regulatory T cells and regulatory B cells (Niedbala et al. 2007, Wang et al. 2014, Egwuagu et al. 2015, Fonseca-Camarillo et al. 2015). This interleukin is secreted and inhibits T cell proliferation (Collison et al. 2007).
This reaction is a black box event because we know the Interleukin-35 heterodimeric protein is secreted but there is no reported evidence from which compartment and which mechanism is involved in the traslocation.

Literature References
PubMed ID Title Journal Year
26279360 Interleukin 35: Critical regulator of immunity and lymphocyte-mediated diseases

Egwuagu, CE, Yu, CR, Sun, L, Wang, R

Cytokine Growth Factor Rev. 2015
18033300 The inhibitory cytokine IL-35 contributes to regulatory T-cell function

Collison, LW, Workman, CJ, Kuo, TT, Boyd, K, Wang, Y, Vignali, KM, Cross, R, Sehy, D, Blumberg, RS, Vignali, DA

Nature 2007
17874423 IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells

Niedbala, W, Wei, XQ, Cai, B, Hueber, AJ, Leung, BP, McInnes, IB, Liew, FY

Eur J Immunol 2007
9342359 Epstein-Barr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin

Devergne, O, Birkenbach, M, Kieff, E

Proc. Natl. Acad. Sci. U.S.A. 1997
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