Glycocode changes in tissues of cancer and autoinflammation, resolution of inflammation, novel immune check-point
Alterations in glycosylation is a hallmark in pathogen recognition by the host which mediates cellular communication during inflammation but also the resolution-phase of inflammation. Homeostatic and inflammatory processes affect the glycan signature of glycoproteins expressed on the cell surface, on secretory proteins, due to up- and down-regulation of glycosylation genes. We study glycan signatures that are recognized by glycan binding receptors such as C-type lectins and siglecs expressed on diverse set of myeloid and lymphoid immune cells, that modify intracellular signalling and immunological outcome. In particular the micro-environmental glycosylation signatures that alter during inflammation such as multiple sclerosis and cancer are studied that drive immune responses towards immunity or tolerance and open new venues for immune interference.
We identified new mechanisms of immune tolerance through the modification of glycosylation of tumours. The analysis of transcriptomic data from patients and tumor cell lines allowed us to identify glycosylations that drive the differentiation programmming of monocytes into tumor associated macrophages (TAMs) upon interaction with tumor cells. Our results show that also in neuroinflammation the glyco-code together with type 2 Macrophages that express C-type lectins drive the resolution phase of autoinflammatory processes such as MS. Also presence of sailic acids regulate increase of FoxP3 CD4+ T cells (Treg) and TAM illustrating immune-suppressive cues sialic acids impose on immune cells.
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