{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T06:12:17Z","timestamp":1779257537332,"version":"3.51.4"},"reference-count":198,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"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:p>Systemic lupus erythematosus (SLE) remains one of the most challenging autoimmune diseases due to its complex pathogenesis involving the breakdown of B cell tolerance. While the PD-1\/PD-L1 axis is traditionally viewed as a universal inhibitory checkpoint, its role in SLE is uniquely nuanced. In this review, we synthesize recent findings to clarify the \u201cPD-1 Paradox\u201d\u2014the observation that high PD-1 expression on pathogenic T follicular helper (Tfh) and T peripheral helper (Tph) cells in SLE patients correlates with chronic activation and extrafollicular expansion rather than functional exhaustion. We also summarize emerging precision immunotherapy strategies, including PD-1 agonists, bispecific inhibitors (targeting ICOSL\/BAFF), and engineered mesenchymal stem cells (MSCs). These interventions aim to move beyond traditional immunosuppression toward a precision \u201creset\u201d of the autoimmune system.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1813842","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:46:15Z","timestamp":1779255975000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bridging B-cell autoimmunity and oncology: the PD-1\/PD-L1 paradox in systemic lupus erythematosus"],"prefix":"10.3389","volume":"17","author":[{"given":"Yunfeng","family":"Guan","sequence":"first","affiliation":[{"name":"Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University","place":["Huzhou, China"]},{"name":"Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University","place":["Huzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Chen","sequence":"additional","affiliation":[{"name":"Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University","place":["Huzhou, China"]},{"name":"Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University","place":["Huzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulong","family":"Hou","sequence":"additional","affiliation":[{"name":"Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University","place":["Huzhou, China"]},{"name":"Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University","place":["Huzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0677-6","article-title":"Autoimmunity and organ 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