Bonura Angela, Vizzini Aiti, Vlah Sara, Gervasi Francesco, Longo Alessandra, Melis Mario R, Schildberg Frank A, Colombo Paolo
Istituto di Biomedicina e di Immunologia Molecolare "Alberto Monroy" del Consiglio Nazionale delle Ricerche, Palermo, Italy.
Marine Immunobiology Laboratory, Department of Biological Chemical Pharmaceutical Science and Technology, University of Palermo, Italy.
Immunobiology. 2018 Feb;223(2):210-219. doi: 10.1016/j.imbio.2017.10.024. Epub 2017 Oct 16.
The selective modulation of immunity is an emerging concept driven by the vast advances in our understanding of this crucial host defense system. Invertebrates have raised researchers' interest as potential sources of new bioactive molecules owing to their antibacterial, anticancer and immunomodulatory activities. A LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates the transcript, Ci8 short, with cis-regulatory elements in the 3' UTR region that are essential for shaping innate immune responses. The derived amino acidic sequence in silico analysis showed specific binding to human Major Histocompatibility Complex (MHC) Class I and Class II alleles. The role of Ci8 short peptide was investigated in a more evolved immune system using human Peripheral Blood Mononuclear Cells (PBMCs) as in vitro model. The biological activities of this molecule include the activation of 70kDa TCR ζ chain Associated Protein kinase (ZAP-70) and T Cell Receptor (TCR) Vβ oligo clonal selection on CD4 T lymphocytes as well as increased proliferation and IFN-γ secretion. Furthermore Ci8 short affects CD4/CD25 induced regulatory T cells (iTreg) subset selection which co-expressed the functional markers TGF-β1/Latency Associated Protein (LAP) and CD39/CD73. This paper describes a new molecule that modulates important responses of the human adaptive immune system.
免疫的选择性调节是一个新兴概念，它是由我们对这一关键宿主防御系统的深入理解所推动的。由于无脊椎动物具有抗菌、抗癌和免疫调节活性，它们作为新生物活性分子的潜在来源引起了研究人员的兴趣。在海鞘肠鳃纲动物中进行脂多糖（LPS）刺激会产生转录本Ci8 short，其3'UTR区域具有顺式调控元件，这些元件对于塑造先天免疫反应至关重要。通过计算机分析得出的氨基酸序列显示，它能与人主要组织相容性复合体（MHC）I类和II类等位基因特异性结合。利用人外周血单个核细胞（PBMCs）作为体外模型，在更进化的免疫系统中研究了Ci8短肽的作用。该分子的生物学活性包括激活70kDa TCR ζ链相关蛋白激酶（ZAP-70）以及对CD4 T淋巴细胞进行T细胞受体（TCR）Vβ寡克隆选择，同时还能促进增殖和增加干扰素-γ分泌。此外，Ci8 short会影响共表达功能性标志物转化生长因子-β1/潜伏相关蛋白（LAP）和CD39/CD73的CD4/CD25诱导调节性T细胞（iTreg）亚群的选择。本文描述了一种调节人类适应性免疫系统重要反应的新分子。
