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

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Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide—Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice. / Nawrocki, Mikołaj; Lory, Niels; Bedke, Tanja; Stumme, Friederike; Diercks, Björn-Phillip; Guse, Andreas H.; Meier, Chris; Gagliani, Nicola; Mittrücker, Hans-Willi; Huber, Samuel.

In: CELLS-BASEL, Vol. 10, No. 11, 3039, 05.11.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Nawrocki, M, Lory, N, Bedke, T, Stumme, F, Diercks, B-P, Guse, AH, Meier, C, Gagliani, N, Mittrücker, H-W & Huber, S 2021, 'Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide—Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice', CELLS-BASEL, vol. 10, no. 11, 3039. https://doi.org/10.3390/cells10113039, https://doi.org/10.3390/cells10113039

APA

Nawrocki, M., Lory, N., Bedke, T., Stumme, F., Diercks, B-P., Guse, A. H., Meier, C., Gagliani, N., Mittrücker, H-W., & Huber, S. (2021). Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide—Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice. CELLS-BASEL, 10(11), [3039]. https://doi.org/10.3390/cells10113039, https://doi.org/10.3390/cells10113039

Vancouver

Nawrocki M, Lory N, Bedke T, Stumme F, Diercks B-P, Guse AH et al. Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide—Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice. CELLS-BASEL. 2021 Nov 5;10(11). 3039. https://doi.org/10.3390/cells10113039, https://doi.org/10.3390/cells10113039

Bibtex

@article{36122f20a3a34622ad1dabac433fa160,
title = "Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide—Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice",
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 na{\"i}ve 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 = "Animals, CD3 Complex/metabolism, Calcium/metabolism, Calcium Signaling/drug effects, Carbolines/pharmacology, Cell Differentiation/drug effects, Cell Plasticity/drug effects, Cell Proliferation/drug effects, Disease Models, Animal, Forkhead Transcription Factors/metabolism, Inflammation/pathology, Interleukin-10/metabolism, Intestines/pathology, Lymphocyte Activation/drug effects, Mice, Inbred C57BL, Mice, Transgenic, NADP/analogs & derivatives, Piperazines/pharmacology, Receptors, Antigen, T-Cell/metabolism, T-Lymphocytes, Regulatory/drug effects, Th1 Cells/drug effects, Th17 Cells/cytology, Up-Regulation/drug effects",
author = "Miko{\l}aj Nawrocki and Niels Lory and Tanja Bedke and Friederike Stumme and Bj{\"o}rn-Phillip Diercks and Guse, {Andreas H.} and Chris Meier and Nicola Gagliani and Hans-Willi Mittr{\"u}cker and Samuel Huber",
year = "2021",
month = nov,
day = "5",
doi = "10.3390/cells10113039",
language = "English",
volume = "10",
journal = "CELLS-BASEL",
issn = "2073-4409",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "11",

}

RIS

TY - JOUR

T1 - Trans-Ned 19-Mediated Antagonism of Nicotinic Acid Adenine Nucleotide—Mediated Calcium Signaling Regulates Th17 Cell Plasticity in Mice

AU - Nawrocki, Mikołaj

AU - Lory, Niels

AU - Bedke, Tanja

AU - Stumme, Friederike

AU - Diercks, Björn-Phillip

AU - Guse, Andreas H.

AU - Meier, Chris

AU - Gagliani, Nicola

AU - Mittrücker, Hans-Willi

AU - Huber, Samuel

PY - 2021/11/5

Y1 - 2021/11/5

N2 - 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.

AB - 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.

KW - Animals

KW - CD3 Complex/metabolism

KW - Calcium/metabolism

KW - Calcium Signaling/drug effects

KW - Carbolines/pharmacology

KW - Cell Differentiation/drug effects

KW - Cell Plasticity/drug effects

KW - Cell Proliferation/drug effects

KW - Disease Models, Animal

KW - Forkhead Transcription Factors/metabolism

KW - Inflammation/pathology

KW - Interleukin-10/metabolism

KW - Intestines/pathology

KW - Lymphocyte Activation/drug effects

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - NADP/analogs & derivatives

KW - Piperazines/pharmacology

KW - Receptors, Antigen, T-Cell/metabolism

KW - T-Lymphocytes, Regulatory/drug effects

KW - Th1 Cells/drug effects

KW - Th17 Cells/cytology

KW - Up-Regulation/drug effects

UR - https://doi.org/10.3390/cells10113039

U2 - 10.3390/cells10113039

DO - 10.3390/cells10113039

M3 - SCORING: Journal article

C2 - 34831261

VL - 10

JO - CELLS-BASEL

JF - CELLS-BASEL

SN - 2073-4409

IS - 11

M1 - 3039

ER -