{"doi":"10.3389/fimmu.2024.1474042","title":"Editorial: O-GlcNAcylation and the immune system","abstract":"Maintenance of immune homeostasis is an intricate biological process involving multiple pathways and molecular mechanisms. One such mechanism is the reversible intracellular posttranslational modification, O-GlcNAcylation. It plays a key role in regulating cell signaling, transcription, and translation, nutrient sensing, metabolism, development, normal physiology, and pathology. Altered O-GlcNAcylation of cellular proteins has been implicated in immune dysfunction leading to the development of autoimmune, inflammatory and allergic diseases as well as malignancies of both immune and non-immune cells. How O-GlcNAcylation regulates the immune system in health and diseases is an emerging area of research and the knowledge on the precise role(s) of O-GlcNAcylated proteins in the immune cells and immune responses is limited (1). This Research Topic includes seven original research articles and six comprehensive review articles covering a broad area on the role of O-GlcNAcylation in the immune system.As an apt prelude to this special topic, Mannino et al., has compiled an excellent beginner's review guide on O-GlcNAcylation as a nutrient sensitive pathway with significant impact on the immune system. This review provides sufficient details on the enzymes regulating O-GlcNAcylation, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), and present O-GlcNAcylation as a nutrient sensing rheostat in the cell. It also discusses how O-GlcNAcylation regulates protein function directly as well as through crosstalk with other protein modifications with implications in the immune system's function, autoimmune and inflammatory diseases as well as immune cell malignancy.Further elaboration on the role of O-GlcNAcylation in immune cell malignancy is provided in the review by Spaner and the original articles by Shu et al., and Schauner et al. Spaner has comprehensively reviewed the effects of O-GlcNAcylation on oncogenic signaling pathways in Chronic Lymphocytic Leukemia (CLL), calling out key regulators such as p53, AKT, NF-kB, RAS, WNT, NOTCH, MYC and STAT proteins, as well as CLL metabolism. Roles of T cells and tumor associated macrophages in CLL are also discussed including details on associated mechanisms. How aberrant O-GlcNAcylation affects other hematological malignancies such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), mantle cell lymphoma (MCL), diffuse large cell lymphoma (DLCL) and multiple myeloma (MM) are also discussed. Informative debates on the functions of O-GlcNAcylation as a tumor promoter or a tumor suppressor and notes on options to block or enhance O-GlcNAcylation as potential therapeutic approaches to treat cancer adds great value to this elegant review.domain-specific OGT (EOGT) expression and immune infiltration. Their results show elevated EOGT expression in tumor infiltrating immune cells, which leads to multiple immune defects including exhausted T cells and immune suppressor cells and lower proportion of cytotoxic T cells in hepatocellular carcinoma (HCC). A large set of bioinformatics data is presented showing EOGT expression in HCC along with immunofluorescent staining of EOGT in normal liver tissue and HCC as validation. Relevant details including different subgroups of EOGT, insight into its biological function, protein-protein interaction network and association between EOGT and immune cell markers are also presented. Although EOGT causes an atypical O-GlcNAcylation in endoplasmic reticulum, it also depends on hexosamine biosynthetic pathway (HBP) and UDP-GlcNAc to modify serine and threonine residues of target proteins. Thus, this study suggests that knowledge on EOGT mediated O-GlcNAcylation may prove relevant to gain a holistic view on the role of HBP and O-GlcNAcylation in immune cell function and cancer.This study shows that expression of key enzymes regulating O-GlcNAcylation are elevated in AML cells compared to healthy blood cells at single cell level and bulk cells. This is a semina","journal":"Frontiers in Immunology","year":2024,"id":487288,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":326799,"name":"Parameswaran Ramakrishnan","orcid":"0000-0002-1314-827X","position":1,"is_corresponding":false},{"id":299280,"name":"Gerald W. Hart","orcid":"0000-0001-7812-4351","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-19T02:08:06.013846Z","pmid":"39229269","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}