{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:06:35Z","timestamp":1793916395295,"version":"4.8.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hypomorphic mutations in the\n                      <jats:italic>phosphoacetylglucosamine mutase 3<\/jats:italic>\n                      (\n                      <jats:italic>PGM3<\/jats:italic>\n                      ) gene cause a glycosylation disorder that leads to immunodeficiency. It is often associated with recurrent infections and atopy. The exact etiology of this condition remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to characterize the phenotypes and immunological features associated with PGM3 insufficiency and investigate potential disease mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review of 44 published cases of PGM3 variants was performed, followed by T-cell phenotyping of two patients with PGM3 variants. A genotype-phenotypic severity study was conducted by comparing the residual PGM3 expression of the 12 reconstituted variants in human B cells. A PGM3 inhibitor was used to assess its effect on CD4+ T cell proliferation and differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with PGM3 variants frequently presented with recurrent infections and atopy, accompanied by reduced na\u00efve CD4+ T cell counts. A genotype\u2013phenotype study showed that low levels of residual PGM3 expression are correlated with disease severity. Notably, inhibition of PGM3 activity impaired TCR-mediated CD4+ T cell proliferation and the synthesis of UDP-GlcNAc, complex N-glycans, O-GlcNAc, glycolytic stress, and mitochondrial respiration during proliferation in a dose-dependent manner. Partial loss of PGM3 activity was observed to preferentially enhance Th1 and Th2 differentiation, while attenuating Th17 and Treg differentiation, consistent with clinical observations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PGM3 is a critical regulator of CD4+ T-cell proliferation and differentiation. These findings provide new insights into the diverse clinical manifestations and therapeutic development of PGM3 deficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1500381","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T01:37:23Z","timestamp":1735004243000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["PGM3 insufficiency: a glycosylation disorder causing a notable T cell 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