Specific and Redundant Roles for NFAT Transcription Factors in the Expression of Mast Cell-Derived Cytokines

Klein, Matthias; Klein-Heßling, Stefan; Palmetshofer, Alois; Serfling, Edgar; Tertilt, Christine; Bopp, Tobias; Heib, Valeska; Becker, Marc A.; Taube, Christian; Schild, Hansjörg; Schmitt, Edgar; Stassen, Michael

doi:10.4049/jimmunol.177.10.6667

Cited by 90 publications

(79 citation statements)

References 48 publications

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“…This observation fits to our previous report showing that IgEmediated degranulation of BMMCs derived from NFATc2-deficient animals is unimpaired, although the expression of some cytokines is severely reduced (27).…”

Section: Nfatc2 Expressed In Mast Cells Is Critical To Initiate Inflasupporting

confidence: 80%

Impaired Mast Cell-Driven Immune Responses in Mice Lacking the Transcription Factor NFATc2

Becker

Heib

Klein

et al. 2009

The Journal of Immunology

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The three calcium-dependent factors NFATc1, c2, and c3 are expressed in cells of the immune system and play pivotal roles in modulating cellular activation. With regard to NFATc2, it was reported that NFATc2-deficient mice display increased immune responses in several models for infection and allergy in vivo. This led to the assumption that NFATc2 is involved in the maintenance of immune homeostasis. Using the synthetic TLR7 agonist imiquimod as an adjuvant in epicutaneous peptide immunization, we observed that both the inflammatory reaction and the peptide-specific CTL response are severely impaired in NFATc2-deficient mice. Detailed analyses revealed that early production of proinflammatory cytokines, lymph node hypertrophy, and migration of Langerhans cells are strongly reduced in NFATc2-deficient animals. With the aid of mast cell-deficient mice and reconstitution experiments using mast cells derived from either NFATc2-deficient mice or wild-type controls, we were able to show that NFATc2 expressed in mast cells is critical for the initiation of inflammation, migration of Langerhans cells, and the development of full-blown CTL responses following epicutaneous immunization. Thus, NFATc2 is an important factor controlling mast cell accessory function at the interface of innate and adaptive immunity.

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Section: Nfatc2 Expressed In Mast Cells Is Critical To Initiate Inflasupporting

confidence: 80%

Impaired Mast Cell-Driven Immune Responses in Mice Lacking the Transcription Factor NFATc2

Becker

Heib

Klein

et al. 2009

The Journal of Immunology

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“…It is well established that NFAT is a major transcription factor that regulates the expression of TNF-␣ and IL-13 (40,46,50). Two isoforms of NFAT, NFAT1/NFATc2 and NFAT2/NFATc1, have been shown to regulate transcription of TNF-␣ and IL-13 in mast cells both individually or in combination, and mast cells deficient in NFAT1/ NFATc2 and NFAT2/NFATc1 have been shown to be severely impaired in the production of TNF-␣ and IL-13 (47). These data support the idea that increase in NFAT levels may contribute to a mechanism for increased cytokine.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, NFATs 1 and 2 (NFATc2 and c1) play important roles in mast cell cytokine production of IL-13 and TNF-␣ triggered by the FcRI (40,46,47). We therefore analyzed mRNA levels of various NFAT isoforms in the WT and Itk Ϫ/Ϫ BMMCs by quantitative RT-PCR.…”

Section: Elevated Nfat Expression and Activation In Itkmentioning

confidence: 99%

The Tec Family Kinase, IL-2-Inducible T Cell Kinase, Differentially Controls Mast Cell Responses

Iyer

August

2008

The Journal of Immunology

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The Tec family tyrosine kinase, IL-2-inducible T cell kinase (Itk), is expressed in T cells and mast cells. Mice lacking Itk exhibit impaired Th2 cytokine secretion; however, they have increased circulating serum IgE, but exhibit few immunological symptoms of allergic airway responses. We have examined the role of Itk in mast cell function and FcεRI signaling. We report in this study that Itk null mice have reduced allergen/IgE-induced histamine release, as well as early airway hyperresponsiveness in vivo. This is due to the increased levels of IgE in the serum of these mice, because the transfer of Itk null bone marrow-derived cultured mast cells into mast cell-deficient W/Wv animals is able to fully rescue histamine release in the W/Wv mice. Further analysis of Itk null bone marrow-derived cultured mast cells in vitro revealed that whereas they have normal degranulation responses, they secrete elevated levels of cytokines, including IL-13 and TNF-α, particularly in response to unliganded IgE. Analysis of biochemical events downstream of the FcεRI revealed little difference in overall tyrosine phosphorylation of specific substrates or calcium responses; however, these cells express elevated levels of NFAT, which was largely nuclear. Our results suggest that the reduced mast cell response in vivo in Itk null mice is due to elevated levels of IgE in these mice. Our results also suggest that Itk differentially modulates mast cell degranulation and cytokine production in part by regulating expression and activation of NFAT proteins in these cells.

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“…Expression of IL-4 and IL-13 is controlled by various transcription factors such as NF-AT1, NF-AT2, GATA-1 and GATA-2 [12,22]. The transcription factor NF-AT is present in a non-activated, i.e., phosphorylated, state in the cytoplasm, and its dephosphorylation is caused by activation of calcineurin, which increases the concentration of Ca Fig.…”

Section: Inhibition Of Nf-at Transcription Factorsmentioning

confidence: 99%

“…NF-AT2 plays an important role in controlling IL-13 transcription along with GATA. GATA-2 promotes IL-13 production in mast cells [22,28]. (Fig.…”

Section: Inhibition Of Gata Transcription Factorsmentioning

confidence: 99%

Double-culture Method Enhances the in Vitro Inhibition of Atopy-inducing Factors by Lactococcus lactis

Jo¹,

Kang²,

Kim³

2015

Journal of Life Science

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We analyzed whether lactic acid bacteria could control the expression of IL-4 and IL-13 in activated mast cells and whether these bacteria could inhibit the activity of transcription factors such as GATA-1, GATA-2, NF-AT1, NF-AT2, and NF-κB p65. We previously described a technique for identification of lactic acid bacteria with anti-atopy functionality by confirming increased expression of CD4+/CD25+/foxp3+ in T cells. We also confirmed that a double-culture method increased the antibacterial activity of these lactic acid bacteria against Staphylococcus aureus (S. aureus). In the present study, we characterized the effect of lactic acid bacteria cultured by this double-culture method on inhibition of allergic inflammatory reactions of RBL-2H3 mast cells, a cellular model of atopic dermatitis. The strongest anti-allergic effects of the lactic acid bacteria were seen in the following order: Lactococcus lactis broth cultured with medium containing Lactobacillus plantarum culture supernatant > Lc. lactis > Lc. lactis broth cultured with medium containing Lb. plantarum culture supernatant > Lb. plantarum. Thus, Lc. lactis cultured in medium containing Lb. plantarum culture supernatant had the strongest inhibitory effect on the differentiation of mast cells during allergic reactions, which may be mediated through the selective regulation of expression of relevant genes.

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Specific and Redundant Roles for NFAT Transcription Factors in the Expression of Mast Cell-Derived Cytokines

Cited by 90 publications

References 48 publications

Impaired Mast Cell-Driven Immune Responses in Mice Lacking the Transcription Factor NFATc2

Impaired Mast Cell-Driven Immune Responses in Mice Lacking the Transcription Factor NFATc2

The Tec Family Kinase, IL-2-Inducible T Cell Kinase, Differentially Controls Mast Cell Responses

Double-culture Method Enhances the in Vitro Inhibition of Atopy-inducing Factors by Lactococcus lactis

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