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Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4(+) T Helper Cell Responses
NLRP11 is a member of the PYD domain-containing, nucleotide-binding oligomerization-domain (NOD-) like receptor (NLR) family. The true stimulus of NLRP11 is still unclear to date, so the current study is built upon NLRP11 induction via adenosine stimulation and that activation can shape adaptive imm...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7421714/ https://www.ncbi.nlm.nih.gov/pubmed/32832566 http://dx.doi.org/10.1155/2020/1421795 |
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author | Ozel, Irem Akkaya, Ilgin Oylumlu, Ece Uzel, Goksu Ciraci, Ceren |
author_facet | Ozel, Irem Akkaya, Ilgin Oylumlu, Ece Uzel, Goksu Ciraci, Ceren |
author_sort | Ozel, Irem |
collection | PubMed |
description | NLRP11 is a member of the PYD domain-containing, nucleotide-binding oligomerization-domain (NOD-) like receptor (NLR) family. The true stimulus of NLRP11 is still unclear to date, so the current study is built upon NLRP11 induction via adenosine stimulation and that activation can shape adaptive immune responses in a caspase-1-independent manner. We examined the regulation and mechanism of adenosine responsiveness via NLRP11 in human Daudi Burkitt's B lymphoma cells and their effects on human peripheral CD4(+) T lymphocytes from healthy individuals. NLRP11 was significantly upregulated after induction with adenosine at both the mRNA and protein levels, which led to the interaction of endogenous NLRP11 with the ASC adaptor protein; however, this interaction did not result in the activation of the caspase-1 enzyme. Furthermore, cocultures of NLRP11-expressing Burkitt's lymphoma cells and naïve human peripheral CD4(+) T lymphocytes had reduced IFN-γ and IL-17A production, whereas IL-13 and IL-10 cytokines did not change. Interestingly, IFN-γ and IL-17A were recovered after transfection of Burkitt's lymphoma cells with siRNAs targeting NLRP11. Concomitant with NLRP11 upregulation, we also exhibited that adenosine A(2B) receptor signaling induced two phosphorylated downstream effectors, pErk1/2 and pAkt (Ser473), but not pAkt (Thr308). Taken together, our data indicate that adenosine is a negative regulator of Th1 and Th17 responses via NLRP11 in an inflammasome-independent manner. |
format | Online Article Text |
id | pubmed-7421714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-74217142020-08-20 Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4(+) T Helper Cell Responses Ozel, Irem Akkaya, Ilgin Oylumlu, Ece Uzel, Goksu Ciraci, Ceren J Immunol Res Research Article NLRP11 is a member of the PYD domain-containing, nucleotide-binding oligomerization-domain (NOD-) like receptor (NLR) family. The true stimulus of NLRP11 is still unclear to date, so the current study is built upon NLRP11 induction via adenosine stimulation and that activation can shape adaptive immune responses in a caspase-1-independent manner. We examined the regulation and mechanism of adenosine responsiveness via NLRP11 in human Daudi Burkitt's B lymphoma cells and their effects on human peripheral CD4(+) T lymphocytes from healthy individuals. NLRP11 was significantly upregulated after induction with adenosine at both the mRNA and protein levels, which led to the interaction of endogenous NLRP11 with the ASC adaptor protein; however, this interaction did not result in the activation of the caspase-1 enzyme. Furthermore, cocultures of NLRP11-expressing Burkitt's lymphoma cells and naïve human peripheral CD4(+) T lymphocytes had reduced IFN-γ and IL-17A production, whereas IL-13 and IL-10 cytokines did not change. Interestingly, IFN-γ and IL-17A were recovered after transfection of Burkitt's lymphoma cells with siRNAs targeting NLRP11. Concomitant with NLRP11 upregulation, we also exhibited that adenosine A(2B) receptor signaling induced two phosphorylated downstream effectors, pErk1/2 and pAkt (Ser473), but not pAkt (Thr308). Taken together, our data indicate that adenosine is a negative regulator of Th1 and Th17 responses via NLRP11 in an inflammasome-independent manner. Hindawi 2020-08-03 /pmc/articles/PMC7421714/ /pubmed/32832566 http://dx.doi.org/10.1155/2020/1421795 Text en Copyright © 2020 Irem Ozel et al. http://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 Ozel, Irem Akkaya, Ilgin Oylumlu, Ece Uzel, Goksu Ciraci, Ceren Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4(+) T Helper Cell Responses |
title | Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4(+) T Helper Cell Responses |
title_full | Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4(+) T Helper Cell Responses |
title_fullStr | Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4(+) T Helper Cell Responses |
title_full_unstemmed | Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4(+) T Helper Cell Responses |
title_short | Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4(+) T Helper Cell Responses |
title_sort | adenosine-induced nlrp11 in b lymphoblasts suppresses human cd4(+) t helper cell responses |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7421714/ https://www.ncbi.nlm.nih.gov/pubmed/32832566 http://dx.doi.org/10.1155/2020/1421795 |
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