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000282555 1001_ $$00009-0001-2018-8747$$aHeyden, Leonie$$b0
000282555 245__ $$aTranscriptional regulator SATB1 limits CD8+ T cell population expansion and effector differentiation in chronic infection and cancer.
000282555 260__ $$aLondon$$bSpringer Nature Limited$$c2025
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000282555 520__ $$aCD8+ T cells are major mediators of antiviral and antitumor immunity. During persistent antigen stimulation as in chronic infection and cancer, however, they differentiate into exhausted T cells that display impaired functionality. Precursors of exhausted T (TPEX) cells exhibit stem-like properties, including high proliferative, self-renewal and developmental potential, and are responsible for long-term CD8+ T cell responses against persistent antigens. Here we identify the chromatin organizer and transcriptional regulator SATB1 as a major regulator of exhausted CD8+ T cell differentiation. SATB1 was specifically expressed in TPEX cells where it limited population expansion and effector differentiation while preserving functionality of CD8+ T cells. SATB1 downregulation was required for TPEX cell-to-effector cell differentiation in chronic infection and contributed to coordinated effector and memory differentiation in acute viral infection. DNA binding of SATB1 regulated gene expression both dependent and independent of chromatin accessibility. Finally, SATB1 limited antitumor CD8+ and chimeric antigen receptor T cell immunity. Overall, our results identify SATB1 as a central regulator of precursor fate and effector differentiation of CD8+ T cells both in infection and in cancer.
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000282555 650_7 $$2NLM Chemicals$$aMatrix Attachment Region Binding Proteins
000282555 650_7 $$2NLM Chemicals$$aSatb1 protein, mouse
000282555 650_7 $$2NLM Chemicals$$aSATB1 protein, human
000282555 650_2 $$2MeSH$$aMatrix Attachment Region Binding Proteins: metabolism
000282555 650_2 $$2MeSH$$aMatrix Attachment Region Binding Proteins: genetics
000282555 650_2 $$2MeSH$$aMatrix Attachment Region Binding Proteins: immunology
000282555 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: immunology
000282555 650_2 $$2MeSH$$aAnimals
000282555 650_2 $$2MeSH$$aCell Differentiation: immunology
000282555 650_2 $$2MeSH$$aMice
000282555 650_2 $$2MeSH$$aImmunologic Memory
000282555 650_2 $$2MeSH$$aMice, Inbred C57BL
000282555 650_2 $$2MeSH$$aNeoplasms: immunology
000282555 650_2 $$2MeSH$$aHumans
000282555 650_2 $$2MeSH$$aPersistent Infection: immunology
000282555 650_2 $$2MeSH$$aLymphocytic Choriomeningitis: immunology
000282555 650_2 $$2MeSH$$aMice, Knockout
000282555 650_2 $$2MeSH$$aCell Proliferation
000282555 650_2 $$2MeSH$$aLymphocytic choriomeningitis virus: immunology
000282555 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
000282555 7001_ $$aRausch, Lisa$$b1
000282555 7001_ $$00009-0006-4257-4629$$aShannon, Michael H$$b2
000282555 7001_ $$00009-0007-5579-7466$$aDryburgh, Lachlan$$b3
000282555 7001_ $$00000-0003-3477-0727$$aMoreira, Marcela L$$b4
000282555 7001_ $$0P:(DE-2719)9002087$$aFrolov, Aleksej$$b5
000282555 7001_ $$00000-0003-3731-6204$$aScheffler, Christina M$$b6
000282555 7001_ $$avan Elsas, Marit J$$b7
000282555 7001_ $$aTong, Junming$$b8
000282555 7001_ $$aHidajat, Olivia$$b9
000282555 7001_ $$00000-0002-0798-6226$$aWijesinghe, Sharanya K M$$b10
000282555 7001_ $$00009-0001-4847-7153$$aLi, Sining$$b11
000282555 7001_ $$00000-0002-4188-4039$$aHorvatic, Helena$$b12
000282555 7001_ $$00009-0002-8152-8351$$aHuynh-Anh, Nhat Truong$$b13
000282555 7001_ $$aGago da Graça, Catarina$$b14
000282555 7001_ $$00000-0003-0642-814X$$aTsui, Carlson$$b15
000282555 7001_ $$0P:(DE-2719)2812698$$aKöhne, Maren$$b16$$udzne
000282555 7001_ $$aSommer, Daniel$$b17
000282555 7001_ $$aWunderlich, F Thomas$$b18
000282555 7001_ $$avon Scheidt, Bianca$$b19
000282555 7001_ $$aPark, Simone L$$b20
000282555 7001_ $$00000-0002-8496-6632$$aMackay, Laura K$$b21
000282555 7001_ $$00000-0003-2205-9057$$aUtzschneider, Daniel T$$b22
000282555 7001_ $$aSchröder, Jan$$b23
000282555 7001_ $$00000-0002-1002-0000$$aTurner, Stephen J$$b24
000282555 7001_ $$00000-0002-5303-9561$$aDarcy, Phillip K$$b25
000282555 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc D$$b26
000282555 7001_ $$aAbdullah, Zeinab$$b27
000282555 7001_ $$00000-0002-6312-6968$$aKallies, Axel$$b28
000282555 773__ $$0PERI:(DE-600)2026412-4$$a10.1038/s41590-025-02316-2$$gVol. 26, no. 12, p. 2312 - 2327$$n12$$p2312 - 2327$$tNature immunology$$v26$$x1529-2908$$y2025
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