Cargando…
Neuropilin-1(high)CD4(+)CD25(+) Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis
Regulatory T cells (Tregs) appear to be involved in sepsis-induced immune dysfunction; neuropilin-1 (Nrp-1) was identified as a surface marker for CD4(+)CD25(+)Tregs. In the current study, we investigated the negative immunoregulation of Nrp-1(high)CD4(+)CD25(+)Tregs and the potential therapeutic va...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863118/ https://www.ncbi.nlm.nih.gov/pubmed/27239104 http://dx.doi.org/10.1155/2016/7132158 |
_version_ | 1782431430794543104 |
---|---|
author | Gao, Yu-Lei Chai, Yan-Fen Qi, An-Long Yao, Ying Liu, Yan-Cun Dong, Ning Wang, Li-Jun Yao, Yong-Ming |
author_facet | Gao, Yu-Lei Chai, Yan-Fen Qi, An-Long Yao, Ying Liu, Yan-Cun Dong, Ning Wang, Li-Jun Yao, Yong-Ming |
author_sort | Gao, Yu-Lei |
collection | PubMed |
description | Regulatory T cells (Tregs) appear to be involved in sepsis-induced immune dysfunction; neuropilin-1 (Nrp-1) was identified as a surface marker for CD4(+)CD25(+)Tregs. In the current study, we investigated the negative immunoregulation of Nrp-1(high)CD4(+)CD25(+)Tregs and the potential therapeutic value of Nrp-1 in sepsis. Splenic CD4(+)CD25(+)Tregs from cecal ligation and puncture (CLP) mouse models were further segregated into Nrp-1(high)Tregs and Nrp-1(low)Tregs; they were cocultured with CD4(+)CD25(−) T cells. The expression of forkhead/winged helix transcription factor-3 (Foxp-3), cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), membrane associated transforming growth factor-β (TGF-β(m+)), apoptotic rate, and secretive ability [including TGF-β and interleukin-10 (IL-10)] for various types of Tregs, as well as the immunosuppressive ability of Tregs on CD4(+)CD25(−) T cells, were determined. Meanwhile, the impact of recombinant Nrp-1 polyclonal antibody on the demethylation of Foxp-3-TSDR (Treg-specific demethylated region) was measured in in vitro study. Sepsis per se markedly promoted the expression of Nrp-1 of CD4(+)CD25(+)Tregs. Foxp-3/CTLA-4/TGF-β(m+) of Nrp-1(high)Tregs were upregulated by septic challenge. Nrp-1(high)Tregs showed strong resilience to apoptosis and secretive ability and the strongest immunosuppressive ability on CD4(+)CD25(−) T cells. In the presence of lipopolysaccharide (LPS), the recombinant Nrp-1 polyclonal antibody reduced the demethylation of Foxp-3-TSDR. Nrp-1(high)Tregs might reveal primary negative immunoregulation in sepsis; Nrp-1 could represent a new potential therapeutic target for the study of immune regulation in sepsis. |
format | Online Article Text |
id | pubmed-4863118 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-48631182016-05-29 Neuropilin-1(high)CD4(+)CD25(+) Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis Gao, Yu-Lei Chai, Yan-Fen Qi, An-Long Yao, Ying Liu, Yan-Cun Dong, Ning Wang, Li-Jun Yao, Yong-Ming Mediators Inflamm Research Article Regulatory T cells (Tregs) appear to be involved in sepsis-induced immune dysfunction; neuropilin-1 (Nrp-1) was identified as a surface marker for CD4(+)CD25(+)Tregs. In the current study, we investigated the negative immunoregulation of Nrp-1(high)CD4(+)CD25(+)Tregs and the potential therapeutic value of Nrp-1 in sepsis. Splenic CD4(+)CD25(+)Tregs from cecal ligation and puncture (CLP) mouse models were further segregated into Nrp-1(high)Tregs and Nrp-1(low)Tregs; they were cocultured with CD4(+)CD25(−) T cells. The expression of forkhead/winged helix transcription factor-3 (Foxp-3), cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), membrane associated transforming growth factor-β (TGF-β(m+)), apoptotic rate, and secretive ability [including TGF-β and interleukin-10 (IL-10)] for various types of Tregs, as well as the immunosuppressive ability of Tregs on CD4(+)CD25(−) T cells, were determined. Meanwhile, the impact of recombinant Nrp-1 polyclonal antibody on the demethylation of Foxp-3-TSDR (Treg-specific demethylated region) was measured in in vitro study. Sepsis per se markedly promoted the expression of Nrp-1 of CD4(+)CD25(+)Tregs. Foxp-3/CTLA-4/TGF-β(m+) of Nrp-1(high)Tregs were upregulated by septic challenge. Nrp-1(high)Tregs showed strong resilience to apoptosis and secretive ability and the strongest immunosuppressive ability on CD4(+)CD25(−) T cells. In the presence of lipopolysaccharide (LPS), the recombinant Nrp-1 polyclonal antibody reduced the demethylation of Foxp-3-TSDR. Nrp-1(high)Tregs might reveal primary negative immunoregulation in sepsis; Nrp-1 could represent a new potential therapeutic target for the study of immune regulation in sepsis. Hindawi Publishing Corporation 2016 2016-04-27 /pmc/articles/PMC4863118/ /pubmed/27239104 http://dx.doi.org/10.1155/2016/7132158 Text en Copyright © 2016 Yu-Lei Gao et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Gao, Yu-Lei Chai, Yan-Fen Qi, An-Long Yao, Ying Liu, Yan-Cun Dong, Ning Wang, Li-Jun Yao, Yong-Ming Neuropilin-1(high)CD4(+)CD25(+) Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis |
title | Neuropilin-1(high)CD4(+)CD25(+) Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis |
title_full | Neuropilin-1(high)CD4(+)CD25(+) Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis |
title_fullStr | Neuropilin-1(high)CD4(+)CD25(+) Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis |
title_full_unstemmed | Neuropilin-1(high)CD4(+)CD25(+) Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis |
title_short | Neuropilin-1(high)CD4(+)CD25(+) Regulatory T Cells Exhibit Primary Negative Immunoregulation in Sepsis |
title_sort | neuropilin-1(high)cd4(+)cd25(+) regulatory t cells exhibit primary negative immunoregulation in sepsis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863118/ https://www.ncbi.nlm.nih.gov/pubmed/27239104 http://dx.doi.org/10.1155/2016/7132158 |
work_keys_str_mv | AT gaoyulei neuropilin1highcd4cd25regulatorytcellsexhibitprimarynegativeimmunoregulationinsepsis AT chaiyanfen neuropilin1highcd4cd25regulatorytcellsexhibitprimarynegativeimmunoregulationinsepsis AT qianlong neuropilin1highcd4cd25regulatorytcellsexhibitprimarynegativeimmunoregulationinsepsis AT yaoying neuropilin1highcd4cd25regulatorytcellsexhibitprimarynegativeimmunoregulationinsepsis AT liuyancun neuropilin1highcd4cd25regulatorytcellsexhibitprimarynegativeimmunoregulationinsepsis AT dongning neuropilin1highcd4cd25regulatorytcellsexhibitprimarynegativeimmunoregulationinsepsis AT wanglijun neuropilin1highcd4cd25regulatorytcellsexhibitprimarynegativeimmunoregulationinsepsis AT yaoyongming neuropilin1highcd4cd25regulatorytcellsexhibitprimarynegativeimmunoregulationinsepsis |