Tolerogenic dendritic cells in the control of autoimmune neuroinflammation: an emerging role of protein-glycan interactions

During the past decade, a great deal of information has contributed to our understanding of the immunosuppressive pathways that operate during the resolution of autoimmune pathology, including central nervous system (CNS) inflammation. Activation of these pathways is accomplished through the integration of an intricate network of inhibitory signals and immune suppressive cells, including regulatory T cells, myeloid-derived suppressor cells, 'alternatively activated' macrophages and tolerogenic dendritic cells (DCs). During the course of inflammatory diseases, immature or mature DCs may be licensed by different stimuli (e.g. cytokines, neuropeptides and growth factors) to become tolerogenic and suppress pathogenic T cell responses, thus emphasizing the outstanding plasticity of these cells. Recent findings have shed light to an immunoregulatory circuit by which galectin-1, an endogenous glycan-binding protein, favors the differentiation of regulatory DCs which promote T cell tolerance and contribute to resolution of autoimmune pathology through mechanisms involving IL-27 and IL-10. Together with the ability of galectin-1-glycan interactions to selectively blunt T helper (Th)1 and Th17 responses, this effect provides a rational explanation for the broad immunosuppressive effects of this glycan-binding protein in several experimental models of chronic inflammation and cancer. In this mini review, we will summarize the regulatory signals leading to the differentiation of tolerogenic DCs and their participation in CNS inflammation. In addition, we will underscore recent findings on the emerging role of galectin-glycan interactions in the establishment of immunosuppressive networks during the resolution of chronic inflammation.Fil: Ilarregui, Juan Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin