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Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders

The emergence of a vaccine against hepatitis B has proven to be an important milestone in the prevention of this disease; however, 5%–10% of vaccinated individuals do not generate an immune response to the vaccine, and its molecular mechanism has not been clarified. In this study, single-cell RNA se...

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Autores principales: Zhao, Meie, Wang, Chunxia, Li, Peiqiang, Sun, Tao, Wang, Jing, Zhang, Shasha, Ma, Qinglong, Ma, Fengdie, Shi, Wenjing, Shi, Maoning, Ma, Yapeng, Pan, Yunyan, Zhang, Hui, Xie, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431960/
https://www.ncbi.nlm.nih.gov/pubmed/37593735
http://dx.doi.org/10.3389/fimmu.2023.1091237
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author Zhao, Meie
Wang, Chunxia
Li, Peiqiang
Sun, Tao
Wang, Jing
Zhang, Shasha
Ma, Qinglong
Ma, Fengdie
Shi, Wenjing
Shi, Maoning
Ma, Yapeng
Pan, Yunyan
Zhang, Hui
Xie, Xiaodong
author_facet Zhao, Meie
Wang, Chunxia
Li, Peiqiang
Sun, Tao
Wang, Jing
Zhang, Shasha
Ma, Qinglong
Ma, Fengdie
Shi, Wenjing
Shi, Maoning
Ma, Yapeng
Pan, Yunyan
Zhang, Hui
Xie, Xiaodong
author_sort Zhao, Meie
collection PubMed
description The emergence of a vaccine against hepatitis B has proven to be an important milestone in the prevention of this disease; however, 5%–10% of vaccinated individuals do not generate an immune response to the vaccine, and its molecular mechanism has not been clarified. In this study, single-cell RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from three volunteers with a high immune response (HR) and three with no immune response (NR) to the hepatitis B vaccine. We found that the antigen-presenting activity scores of various antigen-presenting cells, the mitogen-activated protein kinase (MAPK) pathway activity scores of naive B cells, and the cell activity scores of three types of effector T cells were significantly decreased, whereas the cytotoxicity scores of CD3(high)CD16(low)KLRG1(high) natural killer T (NKT) cells were significantly increased in the NR group compared with those in the HR group. Additionally, the expression levels of some classical molecules associated with distinct signaling pathways—including HLA-B, HLA-DRB5, BLNK, BLK, IL4R, SCIMP, JUN, CEBPB, NDFIP1, and TXNIP—were significantly reduced in corresponding subsets of PBMCs from the NR group relative to those of the HR group. Furthermore, the expression of several cytotoxicity-related effector molecules, such as GNLY, NKG7, GZMB, GZMM, KLRC1, KLRD1, PRF1, CST7, and CTSW, was significantly higher in CD3(high)CD16(low)KLRG1(high) NKT cells derived from non-responders. Our study provides a molecular basis for the lack of response to the hepatitis B vaccine, including defective antigen presentation, decreased T cell activity, and reduced IL-4 secretion, as well as novel insight into the role of NKT cells in the immune response to the hepatitis B vaccine.
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spelling pubmed-104319602023-08-17 Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders Zhao, Meie Wang, Chunxia Li, Peiqiang Sun, Tao Wang, Jing Zhang, Shasha Ma, Qinglong Ma, Fengdie Shi, Wenjing Shi, Maoning Ma, Yapeng Pan, Yunyan Zhang, Hui Xie, Xiaodong Front Immunol Immunology The emergence of a vaccine against hepatitis B has proven to be an important milestone in the prevention of this disease; however, 5%–10% of vaccinated individuals do not generate an immune response to the vaccine, and its molecular mechanism has not been clarified. In this study, single-cell RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from three volunteers with a high immune response (HR) and three with no immune response (NR) to the hepatitis B vaccine. We found that the antigen-presenting activity scores of various antigen-presenting cells, the mitogen-activated protein kinase (MAPK) pathway activity scores of naive B cells, and the cell activity scores of three types of effector T cells were significantly decreased, whereas the cytotoxicity scores of CD3(high)CD16(low)KLRG1(high) natural killer T (NKT) cells were significantly increased in the NR group compared with those in the HR group. Additionally, the expression levels of some classical molecules associated with distinct signaling pathways—including HLA-B, HLA-DRB5, BLNK, BLK, IL4R, SCIMP, JUN, CEBPB, NDFIP1, and TXNIP—were significantly reduced in corresponding subsets of PBMCs from the NR group relative to those of the HR group. Furthermore, the expression of several cytotoxicity-related effector molecules, such as GNLY, NKG7, GZMB, GZMM, KLRC1, KLRD1, PRF1, CST7, and CTSW, was significantly higher in CD3(high)CD16(low)KLRG1(high) NKT cells derived from non-responders. Our study provides a molecular basis for the lack of response to the hepatitis B vaccine, including defective antigen presentation, decreased T cell activity, and reduced IL-4 secretion, as well as novel insight into the role of NKT cells in the immune response to the hepatitis B vaccine. Frontiers Media S.A. 2023-08-01 /pmc/articles/PMC10431960/ /pubmed/37593735 http://dx.doi.org/10.3389/fimmu.2023.1091237 Text en Copyright © 2023 Zhao, Wang, Li, Sun, Wang, Zhang, Ma, Ma, Shi, Shi, Ma, Pan, Zhang and Xie https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhao, Meie
Wang, Chunxia
Li, Peiqiang
Sun, Tao
Wang, Jing
Zhang, Shasha
Ma, Qinglong
Ma, Fengdie
Shi, Wenjing
Shi, Maoning
Ma, Yapeng
Pan, Yunyan
Zhang, Hui
Xie, Xiaodong
Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders
title Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders
title_full Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders
title_fullStr Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders
title_full_unstemmed Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders
title_short Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders
title_sort single-cell rna sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis b vaccine non-responders
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431960/
https://www.ncbi.nlm.nih.gov/pubmed/37593735
http://dx.doi.org/10.3389/fimmu.2023.1091237
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