Ci8 short, a novel LPS-induced peptide from the ascidian Ciona intestinalis, modulates responses of the human immune system.

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 zeta chain Associated Protein kinase (ZAP-70) and T Cell Receptor (TCR) Vbeta oligo clonal selection on CD4+ T lymphocytes as well as increased proliferation and IFN-gamma secretion. Furthermore Ci8 short affects CD4+/CD25high induced regulatory T cells (iTreg) subset selection which co-expressed the functional markers TGF-beta1/Latency Associated Protein (LAP) and CD39/CD73. This paper describes a new molecule that modulates important responses of the human adaptive immune system.