Biology subjects

Aghayev, T.

Publications and source records attributed to Aghayev, T..

3 recordsLinked to original sources

bioRxiv2026

COUNTERING AGE-ASSOCIATED ALTERATIONS IN OLIGODENDROCYTE-DERIVED EXTRACELLULAR MATRIX REJUVENATES COGNITION

Efforts to rejuvenate age-related cognitive decline have predominantly targeted neurons, often overlooking non-neuronal cell types in the aging brain. Here, we show that countering alterations in oligodendrocyte-derived extracellular matrix (ECM) in the aging hippocampus restores cognition. We identify broad age-associated transcriptional and proteomic changes in oligodendrocytes, including dysregulation of the matrisome, with marked upregulation of ECM components and associated regulators with age. Among these, we detect an increase in Hyaluronan and proteoglycan link protein 2 (HAPLN2), an oligodendrocyte-derived core matrisome protein that locates specifically at the nodes of Ranvier, in the hippocampus of aged mice and older humans. Hapln2 overexpression in oligodendrocytes of young mice recapitulated age-related memory impairments. Conversely, abrogating the age-related increase in Hapln2 induced synaptic plasticity-related hippocampal transcriptional signatures and improved memory in aged mice. Together, these data define oligodendrocyte-derived ECM remodeling as a hallmark of brain aging that can be targeted to rescue cognitive decline.

neuroscience↗

bioRxiv2020

IL-27R signaling serves as immunological checkpoint for NK cells to promote hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common form of liver cancer with poor survival and limited therapeutic options. HCC has different etiologies, typically associated with viral or carcinogenic insults or fatty liver disease and underlying chronic inflammation presents as a major unifying mechanism for tumor promotion. On the other hand, mechanisms of how inflammatory response can regulate anti-cancer immunity in HCC remain incompletely understood. Interleukin (IL)-27 receptor signaling plays an anti-inflammatory role in a variety of infectious and chronic inflammatory diseases. Here, using genetic and pharmacological approaches we found that IL-27 receptor (IL-27R) signaling promotes HCC development in vivo. Genetic loss of IL-27R suppressed HCC development in both toxin/carcinogen-induced diethylnitrosamine (DEN) and non-alcoholic steatohepatitis (NASH)-driven models. Elevated expression of IL-27RA rendered poor prognosis to HCC patients. Mechanistically, the pro-tumorigenic effect was mediated by immunoregulatory role of IL-27R signaling within the tumor microenvironment, particularly the suppression of Natural killer (NK) cells. IL-27R ablation enhanced the accumulation and activation of cytotoxic NK cells during acute liver injury and in HCC tumors, while depletion of NK cells abrogated the effect of genetic IL-27R disruption. Taken together, our data suggest an unexpected role of IL-27R signaling as a novel immunological checkpoint regulating NK cell activity and promoting development of HCC of different etiologies.

immunology↗

bioRxiv2019

IL-27 receptor signaling regulated stress myelopoiesis drives Abdominal Aortic Aneurysm development

Abdominal Aortic Aneurysm (AAA) is a vascular disease, where aortic wall degradation is mediated by accumulated immune cells. Though cytokines regulate the inflammatory milieu within the aortic wall, their contribution to AAA through distant alterations, particularly in the control of hematopoietic stem cells proliferation and myeloid cell differentiation remains poorly defined. Here we report an unexpected pathogenic role for interleukin-27 receptor (IL-27R) in AAA development as genetic inactivation of IL-27R protected mice from AAA induced by Angiotensin (Ang) II. The mitigation of AAA in IL-27R deficient mice is associated with a blunted accumulation of myeloid cells in suprarenal aortas due to the surprising attenuation of Ang II-induced expansion of HSCs. The loss of IL-27R engages transcriptional programs that promote HSCs quiescence and suppresses myeloid lineage differentiation, decreasing mature cell production and myeloid cell accumulation in the aorta. We, therefore, illuminate how a prominent vascular disease can be distantly driven by cytokine dependent regulation of the bone marrow precursors.

immunology↗