Details

Autor(en) / Beteiligte

• Morelli, Adrian E.
• Sumpter, Tina L.
• Rojas-Canales, Darling M.
• Bandyopadhyay, Mohna
• Chen, Zhizhao
• Tkacheva, Olga
• Shufesky, William J.
• Wallace, Callen T.
• Watkins, Simon C.
• Berger, Alexandra
• Paige, Christopher J.
• Falo, Louis D.
• Larregina, Adriana T.

Titel

Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells

Ist Teil von

• Cell reports (Cambridge), 2020-03, Vol.30 (10), p.3448-3465.e8

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •T cells express the neurokinin 1 receptor (NK1R) and synthesize its agonists•The NK1R and its agonists co-localize in or near the T cell: APC immune synapse•The NK1R promotes optimal Ca2+ flux and survival of TCR-activated T cells•Lack of the NK1R or its agonists results in deficient Th1-/Th17-biased immunity 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.