2. Academic Validation
  3. Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide-Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice

Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide-Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice

  • Cells. 2021 Nov 5;10(11):3039. doi: 10.3390/cells10113039.
Mikołaj Nawrocki 1 2,  Niels Lory 2 3,  Tanja Bedke 1 2,  Friederike Stumme 1 2,  Björn-Phillip Diercks 4,  Andreas H Guse 4,  Chris Meier 5,  Nicola Gagliani 1 2 6 7,  Hans-Willi Mittrücker 2 3,  Samuel Huber 1 2
Affiliations

Affiliations

  • 1 Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • 2 Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • 3 Institute of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • 4 The Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • 5 Institute of Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany.
  • 6 Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • 7 Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, 17176 Stockholm, Sweden.
PMID: 34831261 DOI: 10.3390/cells10113039
Abstract

Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent CA2+ mobilizing agent and its inhibition proved to inhibit T-cell activation. However, the impact of the NAADP signaling on CD4+ T-cell differentiation and plasticity and on the inflammation in tissues Other than the central nervous system remains unclear. In this study, we used an antagonist of NAADP signaling, trans-Ned 19, to study the role of NAADP in CD4+ T-cell differentiation and effector function. Partial blockade of NAADP signaling in naïve CD4+ T cells in vitro promoted the differentiation of Th17 cells. Interestingly, trans-Ned 19 also promoted the production of IL-10, co-expression of LAG-3 and CD49b and increased the suppressive capacity of Th17 cells. Moreover, using an IL-17A fate mapping mouse model, we showed that NAADP inhibition promotes conversion of Th17 cells into regulatory T cells in vitro and in vivo. In line with the results, we found that inhibiting NAADP ameliorates disease in a mouse model of intestinal inflammation. Thus, these results reveal a novel function of NAADP in controlling the differentiation and plasticity of CD4+ T cells.

Keywords

Ca2+ signaling; NAADP; T cells; adenine nucleotides; immune regulation; immune therapy; inflammatory diseases.

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