{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T05:15:40Z","timestamp":1765516540519,"version":"3.48.0"},"reference-count":14,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"crossref","award":["6-2023-0155"],"award-info":[{"award-number":["6-2023-0155"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Eisai Korea Inc., Seoul, Republic of Korea","award":["4-2024-0700"],"award-info":[{"award-number":["4-2024-0700"]}]},{"name":"Yuhan Corporation, Seoul, Republic of Korea","award":["4-2025-0044"],"award-info":[{"award-number":["4-2025-0044"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objective: This study investigated whether rapamycin could modulate the polarisation of CD4+ T cells towards TH1, TH2, TH17, and Treg cells using peripheral blood mononuclear cell (PBMC) obtained from patients with granulomatosis with polyangiitis and microscopic polyangiitis (GPA\/MPA). Methods: Twenty patients with GPA\/MPA were included in this study. Their stored PBMCs were cultured and stimulated with anti-CD3 and anti-CD28 antibodies for 72 h in the presence or absence of rapamycin (10 nM). The cells were stained for surface markers with anti-CD4-FITC and anti-CD25-APC, followed by intracellular staining using anti-interferon (IFN)-\u03b3-PE, anti-IL-4-PerCP-Cy5, anti-IL17A-APC, and anti-Foxp3-PE. The stained cells were analysed using a flow cytometer. Results: The median age of the 20 GPA\/MPA patients (10 men and 10 women) was 65.5 years. Rapamycin treatment significantly modulated the polarisation of CD4+IFN-\u03b3+ T (TH1) cells compared to no treatment among GPA\/MPA patients. In addition, the polarisation of CD4+IFN-\u03b3+ T (TH1) cells was also significantly reduced in rapamycin-treated PBMC obtained from active patients compared to untreated PBMC from the same patients; however, these alterations were not observed in inactive patients. Conversely, rapamycin treatment did not affect the polarisation of CD4+IL-4+ T (TH2), CD4+IL-17+ T (TH17), or CD4+FoxP3+CD25+ T (Treg) cells, regardless of GPA\/MPA activity. Conclusions: This study was the first pilot study to demonstrate that rapamycin modulates the polarisation of CD4+ T cells towards CD4+IFN-\u03b3+ T cells in active GPA\/MPA.<\/jats:p>","DOI":"10.3390\/jcm14248720","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:51:46Z","timestamp":1765288306000},"page":"8720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rapamycin Modulates the Polarisation of CD4+ T Cells Towards TH1 Cells in Patients with Active Granulomatosis with Polyangiitis and Microscopic Polyangiitis"],"prefix":"10.3390","volume":"14","author":[{"given":"Jang Woo","family":"Ha","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin 16995, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2147-3555","authenticated-orcid":false,"given":"Taejun","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7962-3697","authenticated-orcid":false,"given":"Oh Chan","family":"Kwon","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Beom","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8038-3341","authenticated-orcid":false,"given":"Sang-Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.immuni.2010.09.002","article-title":"The mammalian target of rapamycin: Linking T cell differentiation, function, and metabolism","volume":"33","author":"Powell","year":"2010","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nri3198","article-title":"Regulation and function of mTOR signalling in T cell fate decisions","volume":"12","author":"Chi","year":"2012","journal-title":"Nat. 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