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NFAT c1 deletion in T lymphocytes inhibits the allergic trait in a murine model of asthma
Author(s) -
Koch S.,
Reppert S.,
Finotto S.
Publication year - 2015
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12493
Subject(s) - immunology , immunoglobulin e , nfat , ccl17 , chemokine , biology , ccl13 , t cell , ccl5 , transcription factor , cxcl10 , antibody , immune system , il 2 receptor , gene , biochemistry
Summary Background NFAT c1 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 NFAT c1 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 NFAT c1 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 / CCL 17) by ELISA . Results Mice lacking NFAT c1 in CD 4 + 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 NFAT c1 in T cells in experimental allergic asthma. Conclusions and Clinical Relevance Targeting NFAT c1 in T lymphocytes ameliorated the allergic trait in the airways of NFAT c1 fl/fl x CD 4Cre mice. NFAT c1 emerges as a novel target for anti‐allergy intervention.