NFATc1 induction in peripheral T and B lymphocytes
Matthias Hock,Martin Vaeth,Ronald Rudolf,Amiya K. Patra,Duong Anh Thuy Pham,Khalid Muhammad,Tobias Pusch,Tobias Bopp,Edgar Schmitt,Rene Rost,Friederike Berberich-Siebelt,Dimitri Tyrsin,Sergei Chuvpilo,Andris Avots,Edgar Serfling,Stefan Klein-Hessling +15 more
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TLDR
It is shown that in novel bacterial artificial chromosome transgenic mice that express EGFP under the control of entire Nfatc1 locus the N fatc1/Egfp transgene is expressed as early as in double-negative thymocytes and in nonstimulated peripheral T and B cells.Abstract:
NFAT transcription factors control the proliferation and survival of peripheral lymphocytes. We have reported previously that the short isoform NFATc1/αA whose generation is induced by immune receptor stimulation supports the proliferation and inhibits the activation-induced cell death of peripheral T and B cells. We will show in this study that in novel bacterial artificial chromosome transgenic mice that express EGFP under the control of entire Nfatc1 locus the Nfatc1/Egfp transgene is expressed as early as in double-negative thymocytes and in nonstimulated peripheral T and B cells. Upon immune receptor stimulation, Nfatc1/Egfp expression is elevated in B, Th1, and Th2 cells, but only weakly in T regulatory, Th9, and Th17 cells in vitro whose generation is affected by TGFβ. In naive lymphocytes, persistent immune receptor signals led to a 3-5 increase in NFATc1/αA RNA levels during primary and secondary stimulation, but a much stronger induction was observed at the protein level. Whereas anti-CD3(+)CD28 stimulation of primary T cells induces both NFATc1/αA and their proliferation and survival, anti-IgM stimulation of B cells induces NFATc1/αA and proliferation, but activation-induced cell death after 3-d incubation in vitro. The anti-IgM-mediated activation-induced cell death induction of B cells in vitro is suppressed by anti-CD40-, LPS-, and CpG-mediated signals. In addition to inducing NF-κB factors, together with anti-IgM, these signals also support the generation of NFATc1/αA. According to these data and the architecture of its promoter region, the Nfatc1 gene resembles a primary response gene whose induction is affected at the posttranscriptional level.read more
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Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression
Martin Vaeth,Gerd Müller,Dennis Stauss,Lena Dietz,Stefan Klein-Hessling,Edgar Serfling,Martin Lipp,Ingolf Berberich,Friederike Berberich-Siebelt +8 more
TL;DR: T cell–specific NFAT2 deletion results in reduced CXCR5+ follicular regulatory T cells, leading to uncontrolled germinal center responses and humoral autoimmunity.
Journal ArticleDOI
NFAT control of immune function: New Frontiers for an Abiding Trooper
Martin Vaeth,Stefan Feske +1 more
TL;DR: Novel roles of NFAT in T cells are discussed, focusing mainly on its function in humoral immune responses, immunological tolerance, and the regulation of immune metabolism.
Journal ArticleDOI
NFATc1 controls the cytotoxicity of CD8+ T cells
Stefan Klein-Hessling,Khalid Muhammad,Matthias Klein,Tobias Pusch,Ronald Rudolf,Jessica Flöter,Musga Qureischi,Andreas Beilhack,Martin Vaeth,Martin Vaeth,Carsten Kummerow,Christian S. Backes,Rouven Schoppmeyer,Ulrike Hahn,Markus Hoth,Tobias Bopp,Friederike Berberich-Siebelt,Amiya K. Patra,Amiya K. Patra,Andris Avots,Nora Müller,Almut Schulze,Edgar Serfling +22 more
TL;DR: Genome-wide ChIP-seq data indicate that NFATc1 is an important regulator of cytotoxic T lymphocyte effector functions, and this work shows it controls the cytotoxicity and metabolic switching of activated CD8+ T cells required for optimal response to bacteria and tumor cells.
Journal ArticleDOI
Revisiting the Concept of Targeting NFAT to Control T Cell Immunity and Autoimmune Diseases.
TL;DR: The nuclear factor of activated T cells (NFAT) family of transcription factors, which includes NFAT1, NFAT2, and NFAT4, are well-known to play important roles in T cell activation as mentioned in this paper.
Journal ArticleDOI
Store-Operated Ca(2+) Entry in Follicular T Cells Controls Humoral Immune Responses and Autoimmunity.
Martin Vaeth,Miriam Eckstein,Patrick J. Shaw,Lina Kozhaya,Jun Yang,Friederike Berberich-Siebelt,Robert R. Clancy,Derya Unutmaz,Stefan Feske +8 more
TL;DR: SOCE had a dual role in controlling the GC reaction by regulating both Tfh and Tfr cell differentiation, thus enabling protective B cell responses and preventing humoral autoimmunity.
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