AUTHOR=Alunno Alessia , Bistoni Onelia , Manetti Mirko , Cafaro Giacomo , Valentini Valentina , Bartoloni Elena , Gerli Roberto , Liso Arcangelo 

TITLE=Insulin-Like Growth Factor Binding Protein 6 in Rheumatoid Arthritis: A Possible Novel Chemotactic Factor?

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00554

DOI=10.3389/fimmu.2017.00554

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Objectives</title><p>Immune cell migration from the bloodstream to target tissues is a hallmark of rheumatoid arthritis (RA) pathogenesis. The role of chemoattractants, mainly chemokines, and their possible targeting for therapeutic purposes have been under intense investigation over the last few years but the results were not as satisfactory as expected. The insulin-like growth factor binding protein 6 (IGFBP6), a direct inhibitor of insulin-like growth factor (IGF)-II, also exerts IGF-independent effects including tumor cell migration <italic>in vitro</italic>. We aimed to assess the expression of this protein in serum, synovial fluid, and synovial tissue (ST) of RA patients and to identify its possible chemotactic role in this disorder.</p></sec><sec id="ST2"><title>Methods</title><p>IGFBP6 was measured in RA patients and healthy donors (HD) sera by Luminex xMAP<sup>®</sup> technology and in ST of RA patients and osteoarthritis (OA) controls by immunofluorescence. The identification of circulating IGFBP6<sup>+</sup> cells was evaluated by flow cytometry and an <italic>in vitro</italic> migration assay was arranged.</p></sec><sec id="ST3"><title>Results</title><p>We demonstrated that IGFBP6 is able to induce greater <italic>in vitro</italic> migration of RA as compared to HD and OA T lymphocytes and is overexpressed in serum and ST of RA patients. This <italic>in vitro</italic> chemotactic activity can be partially inhibited by dexamethasone.</p></sec><sec id="ST4"><title>Conclusion</title><p>Our findings suggest a pathogenic role of IGFBP6 in RA and support its possible targeting for therapeutic purposes.</p></sec>