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Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma
BACKGROUND: We recently described increased NFATc1, IRF4, and NIP45 messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMCs) of asthmatic children and adults with multiple allergies. OBJECTIVE: NFATc2 has been described to associate with IRF4 to induce interleukin‐4, and to be i...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654396/ https://www.ncbi.nlm.nih.gov/pubmed/33079489 http://dx.doi.org/10.1002/iid3.360 |
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author | Jakobi, Marielena Kiefer, Alexander Mirzakhani, Hooman Rauh, Manfred Zimmermann, Theodor Xepapadaki, Paraskevi Stanic, Barbara Akdis, Mubeccel Papadopoulos, Nikolaos G. Raby, Benjamin A. Weiss, Scott T. Finotto, Susetta |
author_facet | Jakobi, Marielena Kiefer, Alexander Mirzakhani, Hooman Rauh, Manfred Zimmermann, Theodor Xepapadaki, Paraskevi Stanic, Barbara Akdis, Mubeccel Papadopoulos, Nikolaos G. Raby, Benjamin A. Weiss, Scott T. Finotto, Susetta |
author_sort | Jakobi, Marielena |
collection | PubMed |
description | BACKGROUND: We recently described increased NFATc1, IRF4, and NIP45 messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMCs) of asthmatic children and adults with multiple allergies. OBJECTIVE: NFATc2 has been described to associate with IRF4 to induce interleukin‐4, and to be inhibited by T‐bet. Here, we analyzed the role of NFATc2 in asthmatic children and adults. METHODS: PBMCs were isolated from the blood of control of asthmatics subjects. Some PBMCs were analyzed untreated and some cultured with and without phytohemagglutinin. Then, RNA was extracted from the cells and cytokines were measured in the supernatants via enzyme‐linked immunosorbent assay or multiplex analysis. RNA was then reverse‐transcribed and NFATc1, NFATC2, IRF4, and T‐bet mRNA were analyzed by real‐time polymerase chain reaction. In addition, in peripheral blood cells, NFATc2 expression was analyzed, in a population of asthmatic children and adults from the Asthma BRIDGE study. RESULTS: In addition to NFATc1 and NIP45, also NFATc2 was found upregulated in PBMCs and peripheral blood cells from asthmatic children and adults with allergic asthma. Moreover, NFATc1 directly correlated with lymphocytes number whereas NFATc2 correlated with peripheral eosinophilia in asthma. CONCLUSIONS: In addition to NFATc1 and NIP45, NFATc2 was found upregulated in asthma. Moreover, NFATc1 mRNA correlated with lymphocytes both in control and asthma, and NFATC1 and NFATc2 mRNA showed a direct correlation with eosinophils in controls but not in asthma, indicating that NFATc1 is associated with lymphocytes and not eosinophils in asthma. CLINICAL SIGNIFICANCE: Targeting NFATc2 in T lymphocytes might ameliorate the allergic phenotype in asthmatic subjects. |
format | Online Article Text |
id | pubmed-7654396 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76543962020-11-16 Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma Jakobi, Marielena Kiefer, Alexander Mirzakhani, Hooman Rauh, Manfred Zimmermann, Theodor Xepapadaki, Paraskevi Stanic, Barbara Akdis, Mubeccel Papadopoulos, Nikolaos G. Raby, Benjamin A. Weiss, Scott T. Finotto, Susetta Immun Inflamm Dis Original Research BACKGROUND: We recently described increased NFATc1, IRF4, and NIP45 messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMCs) of asthmatic children and adults with multiple allergies. OBJECTIVE: NFATc2 has been described to associate with IRF4 to induce interleukin‐4, and to be inhibited by T‐bet. Here, we analyzed the role of NFATc2 in asthmatic children and adults. METHODS: PBMCs were isolated from the blood of control of asthmatics subjects. Some PBMCs were analyzed untreated and some cultured with and without phytohemagglutinin. Then, RNA was extracted from the cells and cytokines were measured in the supernatants via enzyme‐linked immunosorbent assay or multiplex analysis. RNA was then reverse‐transcribed and NFATc1, NFATC2, IRF4, and T‐bet mRNA were analyzed by real‐time polymerase chain reaction. In addition, in peripheral blood cells, NFATc2 expression was analyzed, in a population of asthmatic children and adults from the Asthma BRIDGE study. RESULTS: In addition to NFATc1 and NIP45, also NFATc2 was found upregulated in PBMCs and peripheral blood cells from asthmatic children and adults with allergic asthma. Moreover, NFATc1 directly correlated with lymphocytes number whereas NFATc2 correlated with peripheral eosinophilia in asthma. CONCLUSIONS: In addition to NFATc1 and NIP45, NFATc2 was found upregulated in asthma. Moreover, NFATc1 mRNA correlated with lymphocytes both in control and asthma, and NFATC1 and NFATc2 mRNA showed a direct correlation with eosinophils in controls but not in asthma, indicating that NFATc1 is associated with lymphocytes and not eosinophils in asthma. CLINICAL SIGNIFICANCE: Targeting NFATc2 in T lymphocytes might ameliorate the allergic phenotype in asthmatic subjects. John Wiley and Sons Inc. 2020-10-20 /pmc/articles/PMC7654396/ /pubmed/33079489 http://dx.doi.org/10.1002/iid3.360 Text en © 2020 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Jakobi, Marielena Kiefer, Alexander Mirzakhani, Hooman Rauh, Manfred Zimmermann, Theodor Xepapadaki, Paraskevi Stanic, Barbara Akdis, Mubeccel Papadopoulos, Nikolaos G. Raby, Benjamin A. Weiss, Scott T. Finotto, Susetta Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma |
title | Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma |
title_full | Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma |
title_fullStr | Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma |
title_full_unstemmed | Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma |
title_short | Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma |
title_sort | role of nuclear factor of activated t cells 2 (nfatc2) in allergic asthma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654396/ https://www.ncbi.nlm.nih.gov/pubmed/33079489 http://dx.doi.org/10.1002/iid3.360 |
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