{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:23:04Z","timestamp":1790738584121,"version":"4.1.0"},"reference-count":91,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"43","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,10,28]]},"abstract":"<jats:p>B cells orchestrate autoimmune responses in patients with systemic lupus erythematosus (SLE), but broad-based B cell\u2013directed therapies show only modest efficacy while blunting humoral immune responses to vaccines and inducing immunosuppression. Development of more effective therapies targeting pathogenic clones is a currently unmet need. Here, we demonstrate enhanced activation of the ATR\/Chk1 pathway of the DNA damage response (DDR) in B cells of patients with active SLE disease. Treatment of B cells with type I IFN, a key driver of immunity in SLE, induced expression of ATR via binding of interferon regulatory factor 1 to its gene promoter. Pharmacologic targeting of ATR in B cells, via a specific inhibitor (VE-822), attenuated their immunogenic profile, including proinflammatory cytokine secretion, plasmablast formation, and antibody production. Together, these findings identify the ATR-mediated DDR axis as the orchestrator of the type I IFN\u2013mediated B cell responses in SLE and as a potential novel therapeutic target.<\/jats:p>","DOI":"10.1126\/sciadv.abo5840","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T17:58:35Z","timestamp":1666979915000},"source":"Crossref","is-referenced-by-count":40,"title":["ATR-mediated DNA damage responses underlie aberrant B cell activity in systemic lupus erythematosus"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5284-6655","authenticated-orcid":true,"given":"Theodora","family":"Manolakou","sequence":"first","affiliation":[{"name":"Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece."},{"name":"School of Medicine, National and Kapodistrian University of Athens, 115 27 Athens, 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