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IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling
OBJECTIVES: This study aimed to elucidate the changes and associated mechanisms of circulating CD28- cytotoxic T lymphocytes (CTLs) in patients with IgG4-related disease (IgG4-RD). METHODS: Fifty IgG4-RD patients and 15 healthy controls (HCs) were recruited. Peripheral blood mononuclear cells (PBMCs...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301466/ https://www.ncbi.nlm.nih.gov/pubmed/35874706 http://dx.doi.org/10.3389/fimmu.2022.922307 |
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author | Xia, Chang-sheng Long, Yan Liu, Yanying Alifu, Aikede Zeng, Xingyue Liu, Chen |
author_facet | Xia, Chang-sheng Long, Yan Liu, Yanying Alifu, Aikede Zeng, Xingyue Liu, Chen |
author_sort | Xia, Chang-sheng |
collection | PubMed |
description | OBJECTIVES: This study aimed to elucidate the changes and associated mechanisms of circulating CD28- cytotoxic T lymphocytes (CTLs) in patients with IgG4-related disease (IgG4-RD). METHODS: Fifty IgG4-RD patients and 15 healthy controls (HCs) were recruited. Peripheral blood mononuclear cells (PBMCs) were isolated, the levels of circulating CD28- CTLs were detected by flow cytometry, and the proportions of CD127lo or GZMB+CD28- CTL subsets were analyzed in the meantime. Mechanistically, PBMCs isolated from IgG4-RD patients were stimulated with IL-7 in the presence or absence of the JAK inhibitor tofacitinib. Flow cytometry was used to analyze the proliferation of CD28- CTLs and the changes in related subpopulations. RESULTS: Circulating CD4+CD28- CTLs and CD8+CD28- CTLs were significantly increased in IgG4-RD patients compared with HCs, accompanied by an elevation of CD127lo or GZMB+ CTL subsets. The ex vivo culture of PBMCs showed that IL-7 could induce the amplification of CD4+CD28- CTLs and CD8+CD28- CTLs in IgG4-RD. Furthermore, IL-7 promotes the proliferation and functional subset changes of these CD28- CTLs in this disease. The selective JAK inhibitor tofacitinib significantly inhibited the effects of IL-7 on CD4+CD28- CTLs and CD8+CD28- CTLs. CONCLUSION: IL-7 can affect the immune balance of IgG4-RD patients by promoting the expansion and function of CD4+CD28- and CD8+CD28- CTLs in IgG4-RD through the JAK pathway. Blockade of the IL-7 signaling pathway may be a new therapeutic strategy for IgG4-RD. |
format | Online Article Text |
id | pubmed-9301466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93014662022-07-22 IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling Xia, Chang-sheng Long, Yan Liu, Yanying Alifu, Aikede Zeng, Xingyue Liu, Chen Front Immunol Immunology OBJECTIVES: This study aimed to elucidate the changes and associated mechanisms of circulating CD28- cytotoxic T lymphocytes (CTLs) in patients with IgG4-related disease (IgG4-RD). METHODS: Fifty IgG4-RD patients and 15 healthy controls (HCs) were recruited. Peripheral blood mononuclear cells (PBMCs) were isolated, the levels of circulating CD28- CTLs were detected by flow cytometry, and the proportions of CD127lo or GZMB+CD28- CTL subsets were analyzed in the meantime. Mechanistically, PBMCs isolated from IgG4-RD patients were stimulated with IL-7 in the presence or absence of the JAK inhibitor tofacitinib. Flow cytometry was used to analyze the proliferation of CD28- CTLs and the changes in related subpopulations. RESULTS: Circulating CD4+CD28- CTLs and CD8+CD28- CTLs were significantly increased in IgG4-RD patients compared with HCs, accompanied by an elevation of CD127lo or GZMB+ CTL subsets. The ex vivo culture of PBMCs showed that IL-7 could induce the amplification of CD4+CD28- CTLs and CD8+CD28- CTLs in IgG4-RD. Furthermore, IL-7 promotes the proliferation and functional subset changes of these CD28- CTLs in this disease. The selective JAK inhibitor tofacitinib significantly inhibited the effects of IL-7 on CD4+CD28- CTLs and CD8+CD28- CTLs. CONCLUSION: IL-7 can affect the immune balance of IgG4-RD patients by promoting the expansion and function of CD4+CD28- and CD8+CD28- CTLs in IgG4-RD through the JAK pathway. Blockade of the IL-7 signaling pathway may be a new therapeutic strategy for IgG4-RD. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9301466/ /pubmed/35874706 http://dx.doi.org/10.3389/fimmu.2022.922307 Text en Copyright © 2022 Xia, Long, Liu, Alifu, Zeng and Liu 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 Xia, Chang-sheng Long, Yan Liu, Yanying Alifu, Aikede Zeng, Xingyue Liu, Chen IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling |
title | IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling |
title_full | IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling |
title_fullStr | IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling |
title_full_unstemmed | IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling |
title_short | IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling |
title_sort | il-7 promotes the expansion of circulating cd28- cytotoxic t lymphocytes in patients with igg4-related disease via the jak signaling |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301466/ https://www.ncbi.nlm.nih.gov/pubmed/35874706 http://dx.doi.org/10.3389/fimmu.2022.922307 |
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