{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:59:55Z","timestamp":1780898395659,"version":"3.54.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"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>Type 1 diabetes (T1DM) is a T cell-mediated autoimmune disease. The sphingosine-1-phosphate (S1P) signaling pathway regulates lymphocyte trafficking, but its status in T1DM remains poorly characterized. This study investigated S1P and sphingosine-1-phosphate receptor 1(S1PR1) alterations in T1DM through integrated single-cell transcriptomic and clinical analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main methods<\/jats:title>\n                    <jats:p>We performed single-cell RNA sequencing (scRNA-seq)on colonic tissues from T1DM patients and healthy controls, complemented by analysis in non-obese diabetic (NOD) mice at pre-diabetic (4 weeks) and disease stages (12 weeks).Serum total S1P, HDL-bound S1P, and apolipoprotein M (ApoM) were quantified, and transcriptomic functional enrichment of intestinal T cell subsets was further performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      scRNA-seq showed differences in S1P receptor expression in intestinal immune cells between T1DM patients and healthy controls. S1PR1 expression was lower in T cell subsets, particularly CD8+ effector T cells, in T1DM patients. In NOD mice, S1PR1 expression showed a clustered pattern at 4 weeks and was more diffuse with lower levels in lymphocytes at 12 weeks. Clinically, serum total S1P was significantly elevated in T1DM and independently increased T1DM risk, while high-density lipoprotein-bound (HDL-bound) sphingosine-1-phosphate (HDL-S1P) was decreased with unchanged apolipoprotein M (ApoM) levels. Serum S1P positively correlated with glycated hemoglobin (HbA1c) and interleukin-6 (IL-6), and was inversely associated with hypoglycemic episodes. Transcriptomic enrichment indicated functional reprogramming of intestinal CD8\n                      <jats:sup>+<\/jats:sup>\n                      effector T and regulatory T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>T1DM is associated with alterations in the S1P-S1PR1 pathway, characterized by reduced intestinal S1PR1 expression, elevated circulating total S1P, and decreased functional HDL-bound S1P despite stable ApoM.S1P is independently associated with T1DM status and correlates with glycemic control and inflammation, suggesting its potential as a disease-related biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1838952","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:36:31Z","timestamp":1780896991000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Alterations of sphingosine-1-phosphate and its receptors in type 1 diabetes mellitus: an integrated clinical and single-cell transcriptomic study"],"prefix":"10.3389","volume":"17","author":[{"given":"Dongyan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Qilu Hospital of Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]},{"name":"Key Laboratory of Endocrine and Metabolic 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Medicine, Shandong University","place":["Jinan, China"]},{"name":"Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health","place":["Jinan, Shandong, China"]},{"name":"Jinan Clinical Research Center for Endocrine and Metabolic Disease","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]},{"name":"Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health","place":["Jinan, Shandong, China"]},{"name":"Jinan Clinical Research Center for Endocrine and Metabolic Disease","place":["Jinan, Shandong, 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