Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma

• Published in: Immunity, Inflammation and Disease Vol. 8; no. 4; pp. 704 - 712
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2020; John Wiley and Sons Inc; Wiley
• Subjects: Age; Allergens; Allergies; allergy processes; animals; Asthma; Blood; Cell culture; Clinical trials; Collaboration; Data collection; Eosinophils; eosinophils cells; Families & family life; Gene expression; human; Humans; Laboratories; Leukocytes, Mononuclear; Lymphocytes; NFATC Transcription Factors - metabolism; Original Research; Pediatrics; Preschool children; Spirometry; T cells; T-Lymphocytes; Transcription factors; Transplants & implants; Germany; animals; T cells; allergy processes; human; eosinophils cells
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.360

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. In addition to NFATc1 and NIP45, NFATc2 was found upregulated in asthma. Moreover, NFATc1 messenger RNA (mRNA) correlated with lymphocytes both in control and asthma. NFATc2 mRNA showed a direct correlation with eosinophils both in controls and asthma, indicating that NFATc1 is associated with lymphocytes and not eosinophils in asthma.