NFATc1 deletion in T lymphocytes inhibits the allergic trait in a murine model of asthma

Abstract

Background: NFATc1 isoforms are highly regulated in peripheral T cells where they contribute to the effector function and cell homeostasis. Objective: Here, we investigated the role of NFATc1 in asthma and in T cells. Methods: In a murine model of allergic asthma, we analysed differences in T-cell development in this allergic disease model, between wild-type and NFATc1 conditional knockout mice. Thus, we performed quantitative real-time PCR to investigate the mRNA expression of Th2-associated genes as well as genes that are involved in IgE immunoglobulin class-switch. Additionally, we used ELISA, Western blot and flow cytometry (FACS) to analyse protein concentrations of Th1-, Th2- and Th17-specific transcription factors and cytokines and the Th2 chemokine, thymus and activation-regulated chemokine/chemokine ligand 17 (TARC/CCL17) by ELISA. Results: Mice lacking NFATc1 in CD4+ T cells display a significant reduction in lung Th2 and Th17 as well as an increase of Th1 cells in an experimental asthma model. Additionally, Batf gene, a recently described transcription factor of the Th2 and Th17 cell differentiation as well as a key T and B transcription factor involved in the IgE immunoglobulin class-switch, was found decreased in the lungs of these mice. As a consequence, serum OVA-specific IgE and IgG1 levels were found significantly decreased after allergen exposure and in the absence of NFATc1 in T cells in experimental allergic asthma. Conclusions and Clinical Relevance: Targeting NFATc1 in T lymphocytes ameliorated the allergic trait in the airways of NFATc1fl/flxCD4Cre mice. NFATc1 emerges as a novel target for anti-allergy intervention.