An abnormal adherence of monocytes to fibronectin in thyroid autoimmunity has consequences for cell polarization and the development of veiled cells

Blood monocytes of patients with thyroid autoimmune disease (TAID) display defects in rearranging their cortical actomyosin cytoskeleton ('polarize') in response to chemoattractants. Such rearrangements also take place after the adherence of monocytes to the extracellular matrix (ECM). It is therefo re not surprising that monocytes are primed after fibronectin (FN) adherenc e, displaying an enhanced polarization toward chemoattractants. We investigated the integrin expression and chemoattractant-induced polariz ation of monocytes of TAID patients before and after FN adherence. Since cy toskeletal rearrangements are also required during the transition of monocy tes into veiled antigen-presenting cells (VCs), we investigated such transi tion of FN-adherent monocytes of TAID patients. Adherent and nonadherent monocyte populations from TAID patients and health y controls were subjected to a polarization test with the chemoattractant f MLP (or MCP-1), FACS analyses (FITC-labelled FN, CD29, CD49e, d, b and a) a nd tested for their capability to develop into veiled APC. Monocytes of healthy individuals showed an improved chemoattractant-induced cell polarization after FN adherence, not reflected by TAID monocytes, in which chemoattractant-induced polarization worsened. Monocytes of healthy i ndividuals up-regulated CD49e and d integrins and their capability to bind FITC-labelled FN after adherence to a FN-coated plate, as well as enhancing their capability to generate T cell-stimulatory VCs. Monocytes of TAID pat ients did not. These data indicate that integrin- (and chemokine-) mediated functions are hampered in monocytes of TAID patients. Because integrin action is pivotal to processes such as monocyte adherence to endothelial cells, uropod format ion, migration into tissues and differentiation into APC and macrophages, t hese defects might underly immune dysbalances important in thyroid autoimmu ne development.