Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
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
_version_ 1783608060221063168
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
work_keys_str_mv AT jakobimarielena roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT kieferalexander roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT mirzakhanihooman roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT rauhmanfred roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT zimmermanntheodor roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT xepapadakiparaskevi roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT stanicbarbara roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT akdismubeccel roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT papadopoulosnikolaosg roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT rabybenjamina roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT weissscottt roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma
AT finottosusetta roleofnuclearfactorofactivatedtcells2nfatc2inallergicasthma