Zfp281 and Zfp148 control CD4 + T cell thymic development and T H 2 functions.

Autor: Chopp LB; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.; Immunology Graduate Group, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA., Zhu X; Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Gao Y; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Nie J; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Singh J; Single Cell Analysis Facility, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Kumar P; Single Cell Analysis Facility, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Young KZ; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA., Patel S; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.; University of Maryland Medical School, Baltimore, MD 21201, USA., Li C; Flow Cytometry Core, Laboratory of Genomic Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Balmaceno-Criss M; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Vacchio MS; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Wang MM; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.; Neurology Service, VA Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA., Livak F; Flow Cytometry Core, Laboratory of Genomic Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Merchant JL; Department of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tucson, AZ 85724, USA., Wang L; Institute of Immunology, and Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Kelly MC; Single Cell Analysis Facility, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Zhu J; Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Bosselut R; Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2023 Nov 10; Vol. 8 (89), pp. eadi9066. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1126/sciimmunol.adi9066
Abstrakt: How CD4 + lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (T H 2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4 + T cell differentiation of class II major histocompatibility complex (MHC II)-restricted thymocytes, including expression of the CD4 + lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of T H 2 cytokine genes but not of the T H 2 lineage-determining transcription factor Gata3. We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and T H 2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4 + T cell development and T H 2 cell responses.
Databáze: MEDLINE