دورية أكاديمية
أعرض في EDS

Hypermethylation at the CXCR5 gene locus limits trafficking potential of CD8+ T cells into B-cell follicles during HIV-1 infection.

التفاصيل البيبلوغرافية
العنوان: Hypermethylation at the CXCR5 gene locus limits trafficking potential of CD8+ T cells into B-cell follicles during HIV-1 infection.
المؤلفون: Ogunshola FJ; Africa Health Research Institute, Durban, South Africa.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA., Smidt W; Africa Health Research Institute, Durban, South Africa.; KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa., Naidoo AF; HIV Vaccine Trial Network, Cape Town, South Africa., Nkosi T; Africa Health Research Institute, Durban, South Africa.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Ngubane T; Prince Mshiyeni Memorial Hospital, Durban, South Africa., Khaba T; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Baiyegunhi OO; Africa Health Research Institute, Durban, South Africa.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Mahlobo B; Africa Health Research Institute, Durban, South Africa., Rasehlo S; Africa Health Research Institute, Durban, South Africa., Ngema N; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Jajbhay I; Prince Mshiyeni Memorial Hospital, Durban, South Africa., Dong KL; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA., Ramsuran V; KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa., Pansegrouw J; Prince Mshiyeni Memorial Hospital, Durban, South Africa., Ndung'u T; Africa Health Research Institute, Durban, South Africa.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.; Max Planck Institute for Infection Biology, Berlin, Germany., Walker BD; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA.; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.; Howard Hughes Medical Institute, Chevy Chase, MD; and.; Institute for Medical Engineering and Sciences and Department of Biology, Massachusetts Institute of Technology, Cambridge MA., Oliveria T; KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa., Ndhlovu ZM; Africa Health Research Institute, Durban, South Africa.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA.; Prince Mshiyeni Memorial Hospital, Durban, South Africa.
المصدر: Blood advances [Blood Adv] 2022 Mar 22; Vol. 6 (6), pp. 1904-1916.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society of Hematology, [2016]-
مواضيع طبية MeSH: HIV Infections*/genetics , HIV-1*, B-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Humans ; Receptors, CXCR5/genetics ; Receptors, CXCR5/metabolism
مستخلص: CD8+ T cells play an important role in HIV control. However, in human lymph nodes (LNs), only a small subset of CD8+ T cells express CXCR5, the chemokine receptor required for cell migration into B-cell follicles, which are major sanctuaries for HIV persistence in individuals on therapy. Here, we investigate the impact of HIV infection on follicular CD8+ T cell (fCD8) frequencies, trafficking patterns, and CXCR5 regulation. We show that, although HIV infection results in a marginal increase in fCD8s in LNs, the majority of HIV-specific CD8+ T cells are CXCR5- (non-fCD8s) (P < .003). Mechanistic investigations using Assay for Transposase-Accessible Chromatin using sequencing showed that non-fCD8s have closed chromatin at the CXCR5 transcriptional start site (TSS). DNA bisulfite sequencing identified DNA hypermethylation at the CXCR5 TSS as the most probable cause of closed chromatin. Transcriptional factor footprint analysis revealed enrichment of transforming growth factors (TGFs) at the TSS of fCD8s. In vitro stimulation of non-fCD8s with recombinant TGF-β resulted in a significant increase in CXCR5 expression (fCD8s). Thus, this study identifies TGF-β signaling as a viable strategy for increasing fCD8 frequencies in follicular areas of the LN where they are needed to eliminate HIV-infected cells, with implications for HIV cure strategies.
(© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; R01 AI145305 United States AI NIAID NIH HHS; R37 AI067073 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (CXCR5 protein, human)
0 (Receptors, CXCR5)
تواريخ الأحداث: Date Created: 20220106 Date Completed: 20220405 Latest Revision: 20220608
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8941472
DOI: 10.1182/bloodadvances.2021006001
PMID: 34991160
قاعدة البيانات: MEDLINE
الوصف
تدمد:2473-9537
DOI:10.1182/bloodadvances.2021006001