Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells
Summary: Efficient Ca2+ flux induced during cognate T cell activation requires signaling the T cell receptor (TCR) and unidentified G-protein-coupled receptors (GPCRs). T cells express the neurokinin-1 receptor (NK1R), a GPCR that mediates Ca2+ flux in excitable and non-excitable cells. However, the...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720302229 |
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doaj-8754f15be35f40a1af5f7a3af7cdad07 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Adrian E. Morelli Tina L. Sumpter Darling M. Rojas-Canales Mohna Bandyopadhyay Zhizhao Chen Olga Tkacheva William J. Shufesky Callen T. Wallace Simon C. Watkins Alexandra Berger Christopher J. Paige Louis D. Falo, Jr. Adriana T. Larregina |
| spellingShingle |
Adrian E. Morelli Tina L. Sumpter Darling M. Rojas-Canales Mohna Bandyopadhyay Zhizhao Chen Olga Tkacheva William J. Shufesky Callen T. Wallace Simon C. Watkins Alexandra Berger Christopher J. Paige Louis D. Falo, Jr. Adriana T. Larregina Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells Cell Reports |
| author_facet |
Adrian E. Morelli Tina L. Sumpter Darling M. Rojas-Canales Mohna Bandyopadhyay Zhizhao Chen Olga Tkacheva William J. Shufesky Callen T. Wallace Simon C. Watkins Alexandra Berger Christopher J. Paige Louis D. Falo, Jr. Adriana T. Larregina |
| author_sort |
Adrian E. Morelli |
| title |
Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells |
| title_short |
Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells |
| title_full |
Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells |
| title_fullStr |
Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells |
| title_full_unstemmed |
Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells |
| title_sort |
neurokinin-1 receptor signaling is required for efficient ca2+ flux in t-cell-receptor-activated t cells |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2020-03-01 |
| description |
Summary: Efficient Ca2+ flux induced during cognate T cell activation requires signaling the T cell receptor (TCR) and unidentified G-protein-coupled receptors (GPCRs). T cells express the neurokinin-1 receptor (NK1R), a GPCR that mediates Ca2+ flux in excitable and non-excitable cells. However, the role of the NK1R in TCR signaling remains unknown. We show that the NK1R and its agonists, the neuropeptides substance P and hemokinin-1, co-localize within the immune synapse during cognate activation of T cells. Simultaneous TCR and NK1R stimulation is necessary for efficient Ca2+ flux and Ca2+-dependent signaling that sustains the survival of activated T cells and helper 1 (Th1) and Th17 bias. In a model of contact dermatitis, mice with T cells deficient in NK1R or its agonists exhibit impaired cellular immunity, due to high mortality of activated T cells. We demonstrate an effect of the NK1R in T cells that is relevant for immunotherapies based on pro-inflammatory neuropeptides and its receptors. : The neurokinin 1 receptor (NK1R) induces Ca2+ flux in excitable cells. Here, Morelli et al. show that NK1R signaling in T cells promotes optimal Ca2+ flux triggered by TCR stimulation, which is necessary to sustain T cell survival and the efficient Th1- and Th17-based immunity that is relevant for immunotherapies based on pro-inflammatory neuropeptides. Keywords: neurokinin-1 receptor, T cell receptor, G-protein-coupled receptors, Ca2+ flux, Gαq/11, substance P, hemokinin-1, T cell activation, T cell bias, T cell survival |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124720302229 |
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doaj-8754f15be35f40a1af5f7a3af7cdad072020-11-25T00:28:00ZengElsevierCell Reports2211-12472020-03-01301034483465.e8Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T CellsAdrian E. Morelli0Tina L. Sumpter1Darling M. Rojas-Canales2Mohna Bandyopadhyay3Zhizhao Chen4Olga Tkacheva5William J. Shufesky6Callen T. Wallace7Simon C. Watkins8Alexandra Berger9Christopher J. Paige10Louis D. Falo, Jr.11Adriana T. Larregina12Thomas E. Starzl Transplantation Institute, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, School of Medicine Pittsburgh, PA, USADepartment of Immunology, University of Pittsburgh, School of Medicine Pittsburgh, PA, USA; Department of Dermatology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USAFlinders University, College of Medicine and Public Health, Adelaide, SA, AustraliaDepartment of Dermatology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USAHubei Key Laboratory of Medical Technology on Transplantation, Transplant Center, Institute of Hepatobiliary Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, ChinaDepartment of Dermatology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USAThomas E. Starzl Transplantation Institute, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USADepartment of Cell Biology and Center for Biological Imaging, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; The McGowan Center for Regenerative Medicine, Pittsburgh, PA, USADepartment of Immunology, University of Pittsburgh, School of Medicine Pittsburgh, PA, USA; Department of Cell Biology and Center for Biological Imaging, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; The McGowan Center for Regenerative Medicine, Pittsburgh, PA, USAOntario Cancer Institute, Princess Margaret Hospital, Toronto, ON, CanadaOntario Cancer Institute, Princess Margaret Hospital, Toronto, ON, CanadaDepartment of Dermatology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; The McGowan Center for Regenerative Medicine, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA, USA; The University of Pittsburgh Clinical and Translational Science Institute, Pittsburgh, PA, USA; The UPMC Hillman Cancer Center, Pittsburgh, PA, USADepartment of Immunology, University of Pittsburgh, School of Medicine Pittsburgh, PA, USA; Department of Dermatology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; The McGowan Center for Regenerative Medicine, Pittsburgh, PA, USA; Corresponding authorSummary: Efficient Ca2+ flux induced during cognate T cell activation requires signaling the T cell receptor (TCR) and unidentified G-protein-coupled receptors (GPCRs). T cells express the neurokinin-1 receptor (NK1R), a GPCR that mediates Ca2+ flux in excitable and non-excitable cells. However, the role of the NK1R in TCR signaling remains unknown. We show that the NK1R and its agonists, the neuropeptides substance P and hemokinin-1, co-localize within the immune synapse during cognate activation of T cells. Simultaneous TCR and NK1R stimulation is necessary for efficient Ca2+ flux and Ca2+-dependent signaling that sustains the survival of activated T cells and helper 1 (Th1) and Th17 bias. In a model of contact dermatitis, mice with T cells deficient in NK1R or its agonists exhibit impaired cellular immunity, due to high mortality of activated T cells. We demonstrate an effect of the NK1R in T cells that is relevant for immunotherapies based on pro-inflammatory neuropeptides and its receptors. : The neurokinin 1 receptor (NK1R) induces Ca2+ flux in excitable cells. Here, Morelli et al. show that NK1R signaling in T cells promotes optimal Ca2+ flux triggered by TCR stimulation, which is necessary to sustain T cell survival and the efficient Th1- and Th17-based immunity that is relevant for immunotherapies based on pro-inflammatory neuropeptides. Keywords: neurokinin-1 receptor, T cell receptor, G-protein-coupled receptors, Ca2+ flux, Gαq/11, substance P, hemokinin-1, T cell activation, T cell bias, T cell survivalhttp://www.sciencedirect.com/science/article/pii/S2211124720302229 |