Moreover, IC binding to myeloid cells in these conditions was also reported to inhibit their responsiveness to IL-10. In sharp contrast, intravenous administration of soluble immunoglobulins has been used for a long time in the treatment of diverse autoimmune diseases. The immunosuppressive effect of macrophage FccR ligation has been attributed to blocking of the activating FccRs, stimulation of FccRIIb, and increased anti- versus pro-inflammatory cytokine production. Our in vitro data thus support the hypothesis that soluble ICs shift the balance of pro- towards anti-inflammatory cytokine production. Interestingly, this effect may be important not only for the therapeutic efficacy of IVIg, but also of targeted biological therapies. It was indeed recently demonstrated that anti-TNF antibodies induce IL-10 producing macrophages in an Fc-dependent manner and Gelsenicine that these immunoregulatory macrophages are involved in mucosal healing in inflammatory bowel disease. These studies reveal that monoclonal antibody therapy can drive anti-inflammatory responses by Fc region-dependent and target-independent modulation of macrophage function. In conclusion, we showed here that distinct polarized macrophage subsets retain an important functional plasticity despite maintenance of their specific phenotype. In particular, we demonstrated that soluble ICs, but not immobilized IgG shifted the balance of human macrophage cytokine production towards IL-10. These findings raise the possibility of therapeutic modulation of macrophage function in the context of chronic tissue inflammation. Tau is a microtubule-associated protein found predominantly in the central nervous system and expressed mainly in neuronal axons. Tau has six splicing isoforms, ranging in size from 352 to 441 amino acid residues. The shortest tau isoform is expressed only in fetal brain, and the other five are expressed developmentally in the adult brain. Tau drives neurite outgrowth by promoting the assembly of microtubules,Gelsemine which is critical for the establishment of neuronal cell polarity. In Alzheimer’s disease and other neurodegenerative diseases, such as frontotemporal dementia and parkinsonism linked to chromosome 17, tau becomes highly phosphorylated and forms a paired helical filament. Hyperphosphorylated tau-based neurofibrillary lesions are the predominant brain pathology in these disorders, which are referred to collectively as ‘‘tauopathies’’. Leucine-rich repeat kinase 2 is the causative molecule of familial Parkinson’s disease. It is a 286-kDa protein containing an N-terminal leucine-rich repeat, a Ras of complex protein GTPase domain, a C-terminal of the Roc region, a kinase domain, and a WD40 domain. LRRK2 is widely expressed in many organs, such as the brain, heart, kidney, lung, and liver. It is also expressed in some immune cells. In the brain, LRRK2 is expressed in the cerebral cortex, medulla,cerebellum, spinal cord, putamen, and substantia nigra. In the present study, we found for the first time that LRRK2 directly phosphorylates tubulin-associated tau and reduces its tubulin-binding ability, whereas LRRK2 does not phosphorylate the free tau molecule. Thus, LRRK2 would serve as a regulator of association/dissociation between tau and tubulin. In neuronal cells, phosphorylation-dependent dissociation of tau from tubulin is an integral aspect of microtubule dynamics essential for neurite outgrowth and axonal transport, although excessive phosphorylation of tau would negatively regulate its ability to promote microtubule assembly. Therefore, LRRK2 may play an important role in neuronal cell function. Importantly, the PDassociated LRRK2 mutations, G2019S and I2020T, were found to exert hyper-phosphorylation of tau, thus providing a clue for clarifying the mechanism of neurodegeneration.