{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:26:10Z","timestamp":1777501570397,"version":"3.51.4"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"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. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The redox system plays a pivotal role in autoimmune diseases and cancer, with oxidative stress and antioxidant adaptations driving pathological processes. Age\/autoimmunity-associated B cells (ABCs), characterized by elevated ROS levels, are implicated in autoimmune disorders such as systemic lupus erythematosus (SLE). However, the mechanisms linking ROS to ABC differentiation remain unclear. Glutaredoxin 2 (Grx2), a key oxidoreductase, regulates redox homeostasis, but its role in autoimmune B cell biology is underexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using wild-type and Grx2-knockout mice, we examined ROS levels and ABC differentiation. In vitro, ABC differentiation was induced with IL-21 and TLR7 agonist, and the effect of the antioxidant N-Acetyl-L-Cysteine (NAC) was assessed. The SLE-prone Ship\u0394B model crossed with Grx2\u2212\/\u2212 mice was used to evaluate autoimmune pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ABCs exhibited higher ROS levels than follicular B cells, and NAC reduced ABC differentiation rate by 50%, demonstrating ROS dependency. Grx2 deficiency amplified ROS levels and ABC proportions in aged mice, correlating with accelerated autoimmunity. In Ship\u0394B mice, Grx2 deletion exacerbated ABC differentiation, CD4+ T cell activation, and anti-dsDNA autoantibody titers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Grx2 acts as a redox checkpoint that limits ABC-driven autoimmunity by modulating ROS. The Grx2\u2013ROS axis represents a potential therapeutic target for SLE and related chronic inflammatory diseases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1593816","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T05:42:26Z","timestamp":1760506946000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Glutaredoxin2 reduces age-associated B cell differentiation through maintaining redox homeostasis"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuan","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunli","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qilin","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihao","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yatao","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fubin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huihui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1038\/s41590-019-0398-x","article-title":"The immune cell landscape in kidneys of patients with lupus nephritis","volume":"20","author":"Arazi","year":"2019","journal-title":"Nat. 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