Interleukin-27 deletion has neuroprotective effects in the acute ischemic stage of cerebral infarctionFurukawa, Miyake, Ito
et alBiochem Biophys Res Commun (2025) 755, 151581
Abstract: Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. Cytokines such as interleukins 17 and 23 (IL-17, IL-23) have been involved in stroke. IL-27 is a member of the IL-12 family that consists of IL-27p28 and Epstein-Barr virus-induced gene 3 (EBI3), having anti-inflammatory properties and regulating T cell polarization and cytokine production. However, whether IL-27 plays an important role in the acute stage of brain ischemia remains unclear. In the acute stage, IL-27 was upregulated after intracerebral ischemia in wild-type mice while mice lacking IL-27 showed decreased infarction area and suppressed inflammatory cytokines. These findings suggest that IL-27 may be involved in cerebral ischemia and could be a potential therapeutic target for mitigating inflammation and avoiding increasing the initial damage in cerebral ischemia.Copyright © 2025 Elsevier Inc. All rights reserved.
IL35 modulates HBV-related HCC progression via IL6-STAT3 signalingZhou, Xia, Wang
Sci Rep (2025) 15 (1), 6293
Abstract: Hepatocellular carcinoma (HCC) is a common malignant tumor with incidences reported worldwide along with high mortality rates. It is a significant public health concern as hepatitis B virus (HBV) infection is the leading cause of HCC. IL35, a novel heterodimeric cytokine belonging to the IL-12 family, comprises two subunits, namely IL-12p35 and Epstein-Barr virus-induced gene 3 (EBI3). They are crucial in regulating immune responses to tumors and infectious diseases. However, their function in HBV-related HCC is unclear. The objective of this study was to identify the regulatory role of IL35 in the occurrence of HBV-related HCC and its underlying molecular mechanisms. The expression of IL35 was enhanced in human HBV-related HCC tissues. HBV induction, particularly HBx, enhanced the expression of IL-35 in hepatoma cell lines. Silencing IL-35 promoted apoptosis and suppressed proliferation, cell cycle progression, migration, and invasion of HBx-induced hepatoma cells. Mechanistically, silencing IL-35 effectively inhibited the activation of the IL-6-STAT3 signaling pathway by suppressing the expression of IL-6 and nuclear import and phosphorylation of STAT3 in HBx-induced hepatoma cells. Therefore, inhibiting the IL6-STAT3 signaling pathway by silencing IL35 effectively alleviated the progression of HBV-related HCC. IL35 is a potential target for treating HBV-related HCC.© 2025. The Author(s).
Epstein-Barr Virus-Induced 3 Attributes to TLR7-Mediated SplenomegalyIseki, Sakamoto, Takezaki
et alImmunology (2025)
Abstract: Epstein-Barr virus-induced 3 (EBI3) functions as a component of the heterodimer cytokine IL-27, which regulates innate and acquired immune responses. The expression of EBI3 gene is induced by Toll-like receptors (TLRs). Repeated treatment with imiquimod (IMQ), a TLR7 agonist, induces splenomegaly and cytopaenia due to increased splenic function. Although immune cell activation is speculated to play a role in chronic infection-mediated splenomegaly, the detailed mechanisms remain unknown. This study shows that IMQ treatment induces marked splenomegaly and severe bicytopaenia (anaemia and thrombocytopaenia) in wild-type mice. In IMQ-treated mice, myeloid cell populations in the spleen increased, and extramedullary haematopoiesis was observed. RNA-seq analysis revealed the upregulation of type I interferon (IFN)-related genes in the spleens of IMQ-treated mice. IMQ-induced pathological changes were partially mitigated by EBI3 deficiency. To investigate the mechanism of the improved phenotypes in the Ebi3 KO mice, we examined the involvement of IL-27, a heterodimer of EBI3 and IL-27p28. The expression of Il27a, which encodes IL-27p28, was increased in the spleen and peripheral blood by IMQ treatment. Furthermore, IL-27 stimulation upregulated type I IFN-related genes in bone marrow-derived macrophage cultures without type I IFN. These findings suggest that EBI3 deficiency mitigated IMQ-mediated pathological changes, presumably via a lack of IL-27 formation. Our study thus provides insights into the molecular mechanisms underlying chronic infection-mediated splenomegaly.© 2025 John Wiley & Sons Ltd.
Harnessing IL-27: challenges and potential in cancer immunotherapyMaleki, Rajabivahid, Khosh
et alClin Exp Med (2025) 25 (1), 34
Abstract: IL-27 is structurally an immune-enhancing and pleiotropic two-chain cytokine associated with IL-12 and IL-6 families. IL-27 contains two subunits, namely IL-27p28 and EBI3. A heterodimer receptor of IL-27, composed of IL27Rα (WSX1) and IL6ST (gp130) chains, mediates the IL-27 function following the activation of STAT1 and STAT3 signaling pathways. Specifically, IL-27 is identified as augmenting cytokine of immune responses, including Th1 cell differentiation, TCd4 + cell proliferation, and IFN-γ production with the help of IL-12. According to several published studies, due to the pro-inflammatory or anti-inflammatory functions of cytokine related to the biological context in various disorders and diseases, IL-27 has been considered a complex regulator of the immune system. Surprisingly, the dual role of IL-27, the same as the double-edged sword, has also been evidenced in clinical models of various hematological or solid tumors. Predominantly, Il-27 applies anti-tumor functions by inducing the responses of a cytotoxic T lymphocyte (CTL) and Th1 and suppressing the growth, proliferation, angiogenesis, invasiveness, metastasis, and survival of tumor cells. On the other hand, IL-27 may also play a protumor role in cancers and induce tumor progression. The current update study aimed to summarize the protumor anti-tumor and biological functions of IL-27 in different hematological malignancies and solid tumors.© 2025. The Author(s).
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