{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T12:59:18Z","timestamp":1794315558290,"version":"4.9.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","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>Introduction<\/jats:title>\n                    <jats:p>Neuroinflammation is involved in a wide range of neurological disorders, yet the lack of minimally invasive biomarkers hampers early diagnosis and therapeutic monitoring. Glycine receptors (GlyRs), classically known as inhibitory neurotransmitter receptors in the central nervous system, are increasingly recognized as regulators of immune signaling. Here, we identify GlyRs as novel peripheral indicators of neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We demonstrate that GlyR\u03b11, \u03b12, and \u03b13 subunits are constitutively expressed in human and murine immune cells, with GlyR\u03b12 predominating across peripheral tissues and the brain. Using ex vivo and\n                      <jats:italic>in vivo<\/jats:italic>\n                      mouse models, we found that the expression of GlyR\u03b11, \u03b12, and \u03b13 in macrophages and circulating white blood cells (WBCs) was not directly mediated by inflammatory cytokine signaling in the brain or WBCs. Neuroinflammation upregulates GlyR\u03b11 and \u03b13 expression in the brain, spleen, bone marrow, and circulating WBCs. Immunostaining revealed GlyR\u03b13 to the membrane and GlyR\u03b11\/2 to both the membrane and cytoplasm of WBCs. GlyR expression was also observed in the bone marrow, the spleen (macrophage-rich red pulp), and the neurons. Notably, GlyR\u03b11 and \u03b13 expression in WBCs was significantly elevated in neuroinflammation compared to control and systemic inflammation models. Changes in GlyR expression were not correlated with the expression of pro-inflammatory cytokines in the brain and WBCs. LPS-induced microglial (Iba1\n                      <jats:sup>+<\/jats:sup>\n                      ) activation paralleled the upregulation of WBC GlyR, suggesting a reciprocal modulation between central and peripheral compartments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these findings define a brain-glycinergic signaling-blood axis that maintains homeostatic protectivity. GlyR subunits, particularly GlyR\u03b11 and \u03b13, represent a neuropathology-induced modulation of GlyR signaling in peripheral immune cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1749275","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T05:27:40Z","timestamp":1771824460000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Glycine receptors in circulating white blood cells regulated by neuroinflammation"],"prefix":"10.3389","volume":"17","author":[{"given":"Vikram","family":"Thakur","sequence":"first","affiliation":[{"name":"Department of Molecular and Translational Medicine, Paul L. 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Foster School of Medicine, Texas Tech University Health Sciences Center","place":["El Paso, TX, United States"]},{"name":"Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center","place":["El Paso, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakshak","family":"Mishra","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center","place":["El Paso, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osarenoma","family":"Evbuomwan","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center","place":["El Paso, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizbeth","family":"Lopez","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center","place":["El Paso, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center","place":["El Paso, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Chavez","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center","place":["El Paso, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Carrizales","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center","place":["El Paso, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna J.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center","place":["El Paso, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Lavezo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Paul L. 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