bims-stacyt 2019-06-09 papers

Front Immunol. 2019 ;10 1093

Coordination of Immune-Stroma Crosstalk by IL-6 Family Cytokines.

Stromal cells are a subject of rapidly growing immunological interest based on their ability to influence virtually all aspects of innate and adaptive immunity. Present in every bodily tissue, stromal cells complement the functions of classical immune cells by sensing pathogens and tissue damage, coordinating leukocyte recruitment and function, and promoting immune response resolution and tissue repair. These diverse roles come with a price: like classical immune cells, inappropriate stromal cell behavior can lead to various forms of pathology, including inflammatory disease, tissue fibrosis, and cancer. An important immunological function of stromal cells is to act as information relays, responding to leukocyte-derived signals and instructing leukocyte behavior in kind. In this regard, several members of the interleukin-6 (IL-6) cytokine family, including IL-6, IL-11, oncostatin M (OSM), and leukemia inhibitory factor (LIF), have gained recognition as factors that mediate crosstalk between stromal and immune cells, with diverse roles in numerous inflammatory and homeostatic processes. This review summarizes our current understanding of how IL-6 family cytokines control stromal-immune crosstalk in health and disease, and how these interactions can be leveraged for clinical benefit.

Keywords: cytokines; fibrosis; immune; inflammation; stromal cells

DOI: https://doi.org/10.3389/fimmu.2019.01093

FASEB J. 2019 Jun 04. fj201802427RRR

Exosomes from high glucose-treated macrophages activate glomerular mesangial cells via TGF-β1/Smad3 pathway in vivo and in vitro.

Qi-Jin Zhu, Mei Zhu, Xing-Xin Xu, Xiao-Ming Meng, Yong-Gui Wu.

Diabetes nephropathy (DN) is characterized by abnormal interactions between kidney-infiltrating macrophages and glomerular mesangial cells. Recently, a novel cell-cell communication mediated by exosomes has gained attention. Exosomes are membrane-bound vesicles that contain a variety of molecules such as proteins, lipids, DNA, mRNA, and microRNAs. Exosomes play an important role in the pathogenesis of DN. In this study, we show that high glucose (HG) led to increased excretion of exosomes from macrophages. Mesangial cells took up exosomes in vitro, which resulted in the activation and proliferation of mesangial cells and the secretion of extracellular matrix and inflammatory cytokines. In addition, C57BL/6 mice injected with exosomes from HG-treated macrophages showed morphologic and functional changes. We then showed that exosomes from HG-treated TGF-β1 knockdown macrophages induced less extracellular matrix and fewer inflammatory factors in mesangial cells compared with vector control. Our findings suggest that TGF-β1 mRNA in exosomes serves a role between macrophages and mesangial cells by activating the TGF-β1/ mothers against decapentaplegic homolog 3 pathway.-Zhu, Q.-j., Zhu, M., Xu, M.-x., Meng, X.-m., Wu, Y.-g. Exosomes from high glucose-treated macrophages activate glomerular mesangial cells via TGF-β1/Smad3 pathway in vivo and in vitro.

Keywords: activation; diabetic nephropathy; fibrosis; proliferation

DOI: https://doi.org/10.1096/fj.201802427RRR

Aging Dis. 2019 Jun;10(3): 544-556

The Prognostic Value of Serum Cytokines in Patients with Acute Ischemic Stroke.

Xianmei Li, Siyang Lin, Xiaoli Chen, Wensi Huang, Qian Li, Hongxia Zhang, Xudong Chen, Shaohua Yang, Kunlin Jin, Bei Shao.

The inflammatory response is an unavoidable process and contributes to the destruction of cerebral tissue during the acute ischemic stroke (AIS) phase and has not been addressed fully to date. Insightful understanding of correlation of inflammatory mediators and stroke outcome may provide new biomarkers or therapeutic approaches for ischemic stroke. Here, we prospectively recruited 180 first-ever AIS patients within 72 hrs after stroke onset. We used the National Institutes of Health Stroke Scale (NIHSS) to quantify stroke severity and modified Rankin scale (mRS) to assess the 3-month outcome for AIS patients. Initially, we screened 35 cytokines, chemokines, and growth factors in sera from 75 AIS patients and control subjects. Cytokines that were of interest were further investigated in the 180 AIS patients and 14 heathy controls. We found that IL-1RA, IL-1β, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-13, IL-15, EGF, G-CSF, Flt-3L, GM-CSF and Fractalkine levels were significantly decreased in severe stroke patients. In particular, IL-1β, IL-4, IL-5, IL-7, IL-9, IL-10, IL-15, G-CSF and GM-CSF were significantly reduced in AIS patients with poor outcome, compared to those with good prognosis. IL-6 was notably higher in the poor outcome group. Only IL-9 level decreased in the large infarct volume group. After adjusting for confounders, we found that IL-5 was an independent protective factor for prognosis in AIS patients with an adjusted OR of 0.042 (P = 0.007), whereas IL-6 was an independent risk predictor for AIS patients with an adjusted OR of 1.293 (P = 0.003). Our study suggests the levels of serum cytokines are related to stroke severity, short-term prognosis and cerebral infarct volume in AIS patients.

Keywords: acute ischemic stroke; cytokines; inflammation; prognosis; stroke severity

DOI: https://doi.org/10.14336/AD.2018.0820