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Mice expressing catalytically inactive TREX1 (TREX1 D18N) develop lupus\u2010like autoimmunity due to chronic sensing of undegraded TREX1 DNA substrates, production of the inflammatory cytokines, and the inappropriate activation of innate and adaptive immunity. This study aimed to investigate Thelper (Th) dysregulation in the TREX1 D18N model system as a potential mechanism for lupus\u2010like autoimmunity. Comparison of immune cells in secondary lymphoid organs, spleen and peripheral lymph nodes (LNs) between TREX1 D18N mice and the TREX1 null mice revealed that the TREX1 D18N mice exhibit a Th1 bias. Additionally, the T\u2010follicular helper cells (Tfh) and the germinal celter (GC) B cells were also elevated in the TREX1 D18N mice. Targeting Bcl6, a lineage\u2010defining transcription factor for Tfh and GC B cells, with a commercially available Bcl6 inhibitor, FX1, attenuated Tfh, GC, and Th1 responses, and rescued TREX1 D18N mice from autoimmunity. The study presents Tfh and GC B\u2010cell responses as potential targets in autoimmunity and that Bcl6 inhibitors may offer therapeutic approach in TREX1\u2010associated or other lupus\u2010like diseases.<\/jats:p>","DOI":"10.1002\/eji.202149324","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T09:20:18Z","timestamp":1643880018000},"page":"825-834","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting Bcl6 in the TREX1 D18N murine model ameliorates autoimmunity by modulating T\u2010follicular helper cells and germinal center B cells"],"prefix":"10.1002","volume":"52","author":[{"given":"Rajkumar","family":"Venkatadri","sequence":"first","affiliation":[{"name":"Division of Nephrology Department of Medicine Center for Immunity Inflammation and Regenerative Medicine (CIIR), University of Virginia  Charlottesville Virginia United 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