Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide—Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice
Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca<sup>2+</sup> mobilizing agent and its inhibition proved to inhibit T-cell activation. However, the impact of the NAADP signaling on CD4<sup>+</sup> T-cell differentiation and plasticity and on the inf...
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| Autores principales: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/800f263d5f3a4bb294d1ec4fe5002247 |
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| Sumario: | Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca<sup>2+</sup> mobilizing agent and its inhibition proved to inhibit T-cell activation. However, the impact of the NAADP signaling on CD4<sup>+</sup> 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<sup>+</sup> T-cell differentiation and effector function. Partial blockade of NAADP signaling in naïve CD4<sup>+</sup> 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<sup>+</sup> T cells. |
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