Introduction：

While a great deal of research has focused on the role of nucleic acid and protein variation in human disease, the impact of glycosylation changes has been poorly defined.Glycans decorate nearly all proteins in the body, respond rapidly and dramatically to inflammatory cues, and have been centrally implicated inregulating the immune response. With the advent of new technologies, and a great interest in the intersection of glycobiology and immunology, significant advances are now being realized in our understanding of how glycosylation mayboth allow pathogens to subvert the immune system but also represent exciting new targets for the immune system to target for enhanced protection frominfection. Thus in this institutes we proposed to bring together immunology and glycobiology to define the landscape of opportunities by which glycan-based therapeutics can be harnessed for autoimmune, cancer, infectious diseases, and vaccine application.

Our focus：

（1）How glycan binding proteins decode theglycome

Major roles of glycans in health and disease are mediated by binding proteins (GBPs) that decode theinformation content of the glycome through their recognition of glycans asligands. Thus, key to understanding the functions of glycans is elucidation of the functions of GBPs that recognize them. For example, mammalian GBPs aid the immune system to distinguishing between self and nonself. Although there hasbeen a few progress to define the immunological roles of GBPs, the sum of the knowledge to date represents the tip of the iceberg.

(2)The functions of aberrantglycans in antoimmunity

In autoimmunity, aberrant glycosylation can be aneffective diagnostic and prognostic marker. However, the precise contributionof glycan changes to disease progression or even genesis in many of these pathologies remains unclear.

(3) The functions of microbial andhost interactions involving glycans

Although there is a general appreciation that glycans play important roles in both pathogen escapeand, conversely, activation of immune surveillance, a challenge is to provide a more detailed, mechanistic, and holistic understanding of the interplay betweenthe glycosylation of pathogens and their virulence, evolution, and recognition by both innate and adaptive immune responses.

Achievements&significance：

1. Endogenous NKT ligands

Glycans serving as biological ligandsinclude the glycosphingolipid (GSL) recognized by natural killer T (NKT) cells.The identities of endogenous NKT ligands have been an enigma for more than decade. This encouraged us to study the biochemistry of isoglobo series of GSLsin immune organs and immune cells. Furthermore, we and others have found alpha-linked glycosphingolipid, isoglobotriaosylceramide (iGb3),is astimulatory NKT ligand.We discovered that blood group glycolipid(s) are endogenous antigens for iNKT cells maturation inside thymus. These results provide the first evidence that BGL-H is the potential antigen for iNKT cells.

2. Tumor-associated carbohydrate antigens

Glycosphingolipids(GSLs) are information-bearing biomolecules that play critical roles in embryonic development, signal transduction and carcinogenesis. Wediscoveredthat AML patients had higher e­xpression of the GSL lactotriaosylceramide (Lc3), GM3 and neolactotetraosylceramide(nLc4) in their bone marrow than did the healthy donors, especially the M1 subtype of AML andfound that the bone marrow samples of AML patients had 16-fold highere­xpressionof β3Gn-T5 than those of healthy donors. Our results suggest that AML-associated GSLs Lc3 and nLc4 are possibly involved in initiation and differentiation of AML. We performed glycosphingolipidomic assays on neutralGSLs obtained from hepatocellular carcinoma (HCC) tissues and paired peritumoural tissues by ESI mass spectrometry. A group of fucosylated neutral GSLs in HCC was found to be expressed higher in the tumor tissues and seven types offucosylated GSLs were identified, these aberrant GSLs structures mainly contained terminal Fuca2Gal- structure. Our result may lead to improved immunotherapy of HCC and contribute to understanding the role of aberrantfucosylated GSLs in the development and progress of HCC in following studies.

3. Glyco-epitopes expressed by self-tissues and cells lead to autoimmune diseases

Previous studies have reported that altered N-glycosylation occurs in rheumatoid arthritis (RA), particularly the reduction in galactose residues in IgG. To further observe the N-glycans in RAdisease, we showed comprehensive profiling approaches found that the most significant change seen in RA was decreased levels of both mono-galactosyl bi-antennaryN-glycans and dual-galactosyl bi-antennary N-glycans. Our results showed there was a higher e­xpression level of beta galactosidase in RA serum than control. Furthermore, we discovered that there may exist some immonogloblins specificfor redundant agalactosylated N-glycans. We speculate that our preliminary results will provide a promising method both for studies of RA mechanisms and diagnosis.