{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:57:52Z","timestamp":1793649472854,"version":"4.5.1"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Two traditional Chinese medicine (TCM) formulas are Guilu Erxian Glue (GEG) and Danggui Buxue Tang (DBT). Their combination, Modified Guilu Erxian Glue (MGEG), is used to treat aplastic anemia (AA). This study aims to clarify how MGEG restores immune tolerance in AA mice. Specifically, we studied whether MGEG can regulate the differentiation and maturation of T cell lineage by regulating the transcription of miR-146a to rebuild the stable state of bone marrow immune microenvironment, inhibit the immune response mediated by T helper (Th)1 cells, and enhance the immunosuppressive function of regulatory T cells (Tregs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>MGEG\u2019s active constituents and potential targets were identified using HPLC-ESI-MS and network pharmacology. Sublethal irradiation and immune cell infusion were used to create an AA mouse model. Bone marrow histopathology and peripheral blood parameters were used to assess therapeutic efficacy. T cell subsets and the maturation phenotypes of na\u00efve\/effector memory T cells were thoroughly examined using mass cytometry (CyTOF) and flow cytometry. ELISA was used to measure cytokine levels associated with T cell subsets and apoptosis. qPCR quantified miR-146a and its target gene, STAT1, expression levels. The expression levels of important proteins in the STAT1\/SOCS1, Fas\/FasL, and IL-2\/STAT5 signaling pathways as well as lineage-defining transcription factors (T-bet, Foxp3, ROR\u03b3, GATA3) were assessed using Western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Network pharmacology indicated MGEG primarily modulates JAK-STAT and apoptosis pathways.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , MGEG elevated peripheral white blood cell and platelet counts, and alleviated hematopoietic failure. CyTOF and Western blot showed MGEG reprogrammed T cell differentiation: it suppressed Th1\/Th17 cells (downregulating T-bet\/ROR\u03b3) while restoring Foxp3 and promoting an upward trend in GATA3. MGEG boosted na\u00efve T cells and diminished Tem accumulation, reactivating T cell immune reserve. Mechanistically, MGEG upregulated miR-146a, inhibiting the STAT1\/SOCS1 pathway to block Th1-driven inflammation. Concurrently, it modulated Fas\/FasL and IL-2\/STAT5 pathways to inhibit Treg apoptosis and maintain functional stability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MGEG treats AA by constructing a multi-dimensional immunomodulatory network: it suppresses Th1-mediated inflammation via the miR-146a\/STAT1\/SOCS1 axis, preserves Treg function through the IL-2\/STAT5 and Fas\/FasL pathways, and corrects the imbalance between na\u00efve and Tem cells, maintaining long-term immune reserve and homeostasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1826665","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:47:28Z","timestamp":1780030048000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Modified Guilu Erxian Glue restores immune tolerance in aplastic anemia by reprogramming T cell differentiation via the miR-146a\/STAT1\/SOCS1 axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingkai","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongtian","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingmin","family":"Niu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghao","family":"Sang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyang","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing No.6 Hospital, Department of Gastroenterology","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Hospital of Traditional Chinese Medicine, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Chai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen 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