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Hobit and Blimp-1 regulate T RM abundance after LCMV infection by suppressing tissue exit pathways of T RM precursors

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2022

Eur J Immunol. 2022 Apr 7. doi: 10.1002/eji.202149665. Online ahead of print.

Hobit and Blimp-1 regulate T RM abundance after LCMV infection by suppressing tissue exit pathways of T RM precursors

Loreto Parga-Vidal, Renske L R E Taggenbrock, Ammarina Beumer-Chuwonpad, Hajar Aglmous, Natasja A M Kragten, Felix M Behr, Astrid A Bovens, Rene A W van Lier, Regina Stark, Klaas P J M van Gisbergen

Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Germany.

Service type: Knock-in mice

Abstract

Tissue-resident memory T cells (Trm) are retained in peripheral tissues after infection for enhanced protection against secondary encounter with the same pathogen. We have previously shown that the transcription factor Hobit and its homolog Blimp-1 drive Trm development after viral infection, but how and when these transcription factors mediate Trm formation remains poorly understood. In particular, the major impact of Blimp-1 in regulating several aspects of effector T-cell differentiation impairs study of its specific role in Trm development. Here, we used the restricted expression of Hobit in the Trm lineage to develop mice with a conditional deletion of Blimp-1 in Trm, allowing us to specifically investigate the role of both transcription factors in Trm differentiation. We found that Hobit and Blimp-1 were required for the upregulation of CD69 and suppression of CCR7 and S1PR1 on virus-specific Trm precursors after LCMV infection, underlining a role in their retention within tissues. The early impact of Hobit and Blimp-1 favored Trm formation and prevented the development of circulating memory T cells. Thus, our findings highlight a role of Hobit and Blimp-1 at the branching point of circulating and resident memory lineages by suppressing tissue egress of Trm precursors early during infection.

Keywords: Blimp-1; CD8+ T-cell differentiation; Hobit; LCMV; tissue-resident memory CD8+ T cells.

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