Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation.

Autor: Buquicchio FA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA., Fonseca R; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Yan PK; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA., Wang F; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA., Evrard M; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Obers A; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Gutierrez JC; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA., Raposo CJ; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA., Belk JA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA., Daniel B; Department of Pathology, Stanford University, Stanford, CA 94305, USA., Zareie P; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Yost KE; Department of Pathology, Stanford University, Stanford, CA 94305, USA., Qi Y; Department of Pathology, Stanford University, Stanford, CA 94305, USA., Yin Y; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA., Nico KF; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA., Tierney FM; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA., Howitt MR; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA., Lareau CA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA; Parker Institute for Cancer Immunotherapy, Stanford University, Stanford, CA 94129, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA., Satpathy AT; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA; Parker Institute for Cancer Immunotherapy, Stanford University, Stanford, CA 94129, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA. Electronic address: satpathy@stanford.edu., Mackay LK; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia. Electronic address: lkmackay@unimelb.edu.au.
Jazyk: angličtina
Zdroj: Immunity [Immunity] 2024 Sep 10; Vol. 57 (9), pp. 2202-2215.e6. Date of Electronic Publication: 2024 Jul 22.
DOI: 10.1016/j.immuni.2024.06.014
Abstrakt: The memory CD8 + T cell pool contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. Here, we examined the epigenetic landscape of CD8 + T cells isolated from seven non-lymphoid organs across four distinct infection models, alongside their circulating T cell counterparts. Using single-cell transposase-accessible chromatin sequencing (scATAC-seq), we found that tissue-resident memory T (T RM ) cells and circulating memory T (T CIRC ) cells develop along distinct epigenetic trajectories. We identified organ-specific transcriptional regulators of T RM cell development, including FOSB, FOS, FOSL1, and BACH2, and defined an epigenetic signature common to T RM cells across organs. Finally, we found that although terminal T EX cells share accessible regulatory elements with T RM cells, they are defined by T EX -specific epigenetic features absent from T RM cells. Together, this comprehensive data resource shows that T RM cell development is accompanied by dynamic transcriptome alterations and chromatin accessibility changes that direct tissue-adapted and functionally distinct T cell states.
Competing Interests: Declaration of interests A.T.S. is a founder of Immunai, Cartography Biosciences, Santa Ana Bio, and Prox Biosciences and receives research funding from Merck Research Laboratories, Allogene Therapeutics, and Astellas Pharma. K.E.Y. is a consultant for Cartography Biosciences.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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