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CD4(+) T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE
OBJECTIVE: To explore cooperation between activated naïve (aNAV) B cells and CD4(+) T cells in the pathogenesis of SLE through autoantibody production, T-cell differentiation and inflammatory cytokine secretion. METHODS: Peripheral blood mononuclear cell samples were obtained from 31 patients with S...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9528597/ https://www.ncbi.nlm.nih.gov/pubmed/36180106 http://dx.doi.org/10.1136/lupus-2022-000739 |
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author | Wangriatisak, Kittikorn Kochayoo, Piyawan Thawornpan, Pongsakorn Leepiyasakulchai, Chaniya Suangtamai, Thanitta Ngamjanyaporn, Pintip Khowawisetsut, Ladawan Khaenam, Prasong Pisitkun, Prapaporn Chootong, Patchanee |
author_facet | Wangriatisak, Kittikorn Kochayoo, Piyawan Thawornpan, Pongsakorn Leepiyasakulchai, Chaniya Suangtamai, Thanitta Ngamjanyaporn, Pintip Khowawisetsut, Ladawan Khaenam, Prasong Pisitkun, Prapaporn Chootong, Patchanee |
author_sort | Wangriatisak, Kittikorn |
collection | PubMed |
description | OBJECTIVE: To explore cooperation between activated naïve (aNAV) B cells and CD4(+) T cells in the pathogenesis of SLE through autoantibody production, T-cell differentiation and inflammatory cytokine secretion. METHODS: Peripheral blood mononuclear cell samples were obtained from 31 patients with SLE and used to characterise phenotype of aNAV B cells (n=14) and measured the phosphorylation of B-cell receptor (BCR) signalling molecules (n=5). Upregulation of T-cell costimulatory molecules after BCR and toll-like receptor (TLR)-7/TLR-8 stimulation was detected in cells from four subjects. To explore the role of these cells in SLE pathogenesis via T cell-dependent mechanisms, four subjects were analysed to detect the promotion of CD4(+) T-cell activation and antibody-secreting cell (ASC) differentiation after CD4(+) T-cell–B-cell cocultures. The aNAV B cells from four patients were used to assess cytokine secretion. RESULTS: The aNAV B cells of patients with SLE had increased expression of surface CD40, HLA-DR and interleukin-21 receptor (IL-21R) and FCRL5 molecules. With BCR stimulation, these cells greatly increased PLCγ2 phosphorylation. Integrated BCR and TLR-7/TLR-8 signals induced overexpression of CD40, CD86, IL-21R and HLA-DR on lupus aNAV B cells. In T-cell–B-cell cocultures, lupus aNAV B cells (with upregulated costimulatory molecules) promoted CD4(+) T-cell proliferation and polarisation toward effector Th(2) and Th(17) cells. Importantly, in this coculture system, CD4(+) T-cell signals enhanced aNAV B-cell differentiation into auto-ASCs and produced anti-DNA antibodies. The interaction between CD4(+) T cell and aNAV B cell increased production of inflammatory cytokines (IL-6, IL-8 and IL-23). CONCLUSION: Cooperation between aNAV B cells and CD4(+) T cells contributed to SLE pathogenesis by promoting both differentiation of pathogenic T cells (Th(2) and Th(17)) and autoantibody secretion. |
format | Online Article Text |
id | pubmed-9528597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-95285972022-10-04 CD4(+) T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE Wangriatisak, Kittikorn Kochayoo, Piyawan Thawornpan, Pongsakorn Leepiyasakulchai, Chaniya Suangtamai, Thanitta Ngamjanyaporn, Pintip Khowawisetsut, Ladawan Khaenam, Prasong Pisitkun, Prapaporn Chootong, Patchanee Lupus Sci Med Immunology and Inflammation OBJECTIVE: To explore cooperation between activated naïve (aNAV) B cells and CD4(+) T cells in the pathogenesis of SLE through autoantibody production, T-cell differentiation and inflammatory cytokine secretion. METHODS: Peripheral blood mononuclear cell samples were obtained from 31 patients with SLE and used to characterise phenotype of aNAV B cells (n=14) and measured the phosphorylation of B-cell receptor (BCR) signalling molecules (n=5). Upregulation of T-cell costimulatory molecules after BCR and toll-like receptor (TLR)-7/TLR-8 stimulation was detected in cells from four subjects. To explore the role of these cells in SLE pathogenesis via T cell-dependent mechanisms, four subjects were analysed to detect the promotion of CD4(+) T-cell activation and antibody-secreting cell (ASC) differentiation after CD4(+) T-cell–B-cell cocultures. The aNAV B cells from four patients were used to assess cytokine secretion. RESULTS: The aNAV B cells of patients with SLE had increased expression of surface CD40, HLA-DR and interleukin-21 receptor (IL-21R) and FCRL5 molecules. With BCR stimulation, these cells greatly increased PLCγ2 phosphorylation. Integrated BCR and TLR-7/TLR-8 signals induced overexpression of CD40, CD86, IL-21R and HLA-DR on lupus aNAV B cells. In T-cell–B-cell cocultures, lupus aNAV B cells (with upregulated costimulatory molecules) promoted CD4(+) T-cell proliferation and polarisation toward effector Th(2) and Th(17) cells. Importantly, in this coculture system, CD4(+) T-cell signals enhanced aNAV B-cell differentiation into auto-ASCs and produced anti-DNA antibodies. The interaction between CD4(+) T cell and aNAV B cell increased production of inflammatory cytokines (IL-6, IL-8 and IL-23). CONCLUSION: Cooperation between aNAV B cells and CD4(+) T cells contributed to SLE pathogenesis by promoting both differentiation of pathogenic T cells (Th(2) and Th(17)) and autoantibody secretion. BMJ Publishing Group 2022-09-30 /pmc/articles/PMC9528597/ /pubmed/36180106 http://dx.doi.org/10.1136/lupus-2022-000739 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Immunology and Inflammation Wangriatisak, Kittikorn Kochayoo, Piyawan Thawornpan, Pongsakorn Leepiyasakulchai, Chaniya Suangtamai, Thanitta Ngamjanyaporn, Pintip Khowawisetsut, Ladawan Khaenam, Prasong Pisitkun, Prapaporn Chootong, Patchanee CD4(+) T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE |
title | CD4(+) T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE |
title_full | CD4(+) T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE |
title_fullStr | CD4(+) T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE |
title_full_unstemmed | CD4(+) T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE |
title_short | CD4(+) T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE |
title_sort | cd4(+) t-cell cooperation promoted pathogenic function of activated naïve b cells of patients with sle |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9528597/ https://www.ncbi.nlm.nih.gov/pubmed/36180106 http://dx.doi.org/10.1136/lupus-2022-000739 |
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