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

Morelli, Adrián E.; Sumpter, Tina L.; Rojas-Canales, Darling; 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.

doi:10.1016/j.celrep.2020.02.054

Cited by 26 publications

(35 citation statements)

References 90 publications

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“…Especially, NK1R is known to mainly contribute to transmission of pruritus ( 4 , 12 , 147 ). NK1R is widely expressed by different immune cells, such as dendritic cells ( 148 ), eosinophils ( 149 ), mast cells ( 150 ), macrophages and monocytes ( 151 ) and T and B cells ( 152 , 153 ), but also by keratinocytes ( 154 , 155 ) and sensory nerve endings ( 11 , 156 , 157 ). Activation of NK1R via SP leads to multiple signaling cascades involving mast cell degranulation and release of proinflammatory mediators, such as histamine, nerve growth factor expression and leukotriene B4 in keratinocytes and neurogenic inflammation resulting in induction of inflammation and pruritus ( 145 , 146 , 158 ).…”

Section: Receptors In Neuro-immune Interactionsmentioning

confidence: 99%

Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

et al. 2021

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Pruritus is a common, but very challenging symptom with a wide diversity of underlying causes like dermatological, systemic, neurological and psychiatric diseases. In dermatology, pruritus is the most frequent symptom both in its acute and chronic form (over 6 weeks in duration). Treatment of chronic pruritus often remains challenging. Affected patients who suffer from moderate to severe pruritus have a significantly reduced quality of life. The underlying physiology of pruritus is very complex, involving a diverse network of components in the skin including resident cells such as keratinocytes and sensory neurons as well as transiently infiltrating cells such as certain immune cells. Previous research has established that there is a significant crosstalk among the stratum corneum, nerve fibers and various immune cells, such as keratinocytes, T cells, basophils, eosinophils and mast cells. In this regard, interactions between receptors on cutaneous and spinal neurons or on different immune cells play an important role in the processing of signals which are important for the transmission of pruritus. In this review, we discuss the role of various receptors involved in pruritus and inflammation, such as TRPV1 and TRPA1, IL-31RA and OSMR, TSLPR, PAR-2, NK1R, H1R and H4R, MRGPRs as well as TrkA, with a focus on interaction between nerve fibers and different immune cells. Emerging evidence shows that neuro-immune interactions play a pivotal role in mediating pruritus-associated inflammatory skin diseases such as atopic dermatitis, psoriasis or chronic spontaneous urticaria. Targeting these bidirectional neuro-immune interactions and the involved pruritus-specific receptors is likely to contribute to novel insights into the underlying pathogenesis and targeted treatment options of pruritus.

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Section: Receptors In Neuro-immune Interactionsmentioning

confidence: 99%

Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

et al. 2021

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“… Voedisch et al (2012) TRPV1 + sensory nerves produce and store SP in the large-DCV. This NP is not only released from these neurons upon allergen stimulus ( He et al, 2019 ; Perner et al, 2020 ), it can also be synthesized by non-neuronal cells, such as lymphocytes ( Morelli et al, 2020 ), DC, eosinophils ( Lambrecht et al, 1999 ), and macrophages ( Ho et al, 1997 ). Once exocytosed from the neuronal soma or axonal terminals, it couples to its specific receptor (Neurokinin receptors -NKRs-), belongs to the GPCR family ( Badri and Smith, 2019 ), expressed either on the same cell or on the neighboring cells (epithelial, endothelial, ASM cells, fibroblasts, and immune cells).…”

Section: Substance Pmentioning

confidence: 99%

Neuroimmune Pathophysiology in Asthma

Pavón-Romero

Serrano-Pérez

García-Sánchez

et al. 2021

Front. Cell Dev. Biol.

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Asthma is a chronic inflammation of lower airway disease, characterized by bronchial hyperresponsiveness. Type I hypersensitivity underlies all atopic diseases including allergic asthma. However, the role of neurotransmitters (NT) and neuropeptides (NP) in this disease has been less explored in comparison with inflammatory mechanisms. Indeed, the airway epithelium contains pulmonary neuroendocrine cells filled with neurotransmitters (serotonin and GABA) and neuropeptides (substance P[SP], neurokinin A [NKA], vasoactive intestinal peptide [VIP], Calcitonin-gene related peptide [CGRP], and orphanins-[N/OFQ]), which are released after allergen exposure. Likewise, the autonomic airway fibers produce acetylcholine (ACh) and the neuropeptide Y(NPY). These NT/NP differ in their effects; SP, NKA, and serotonin exert pro-inflammatory effects, whereas VIP, N/OFQ, and GABA show anti-inflammatory activity. However, CGPR and ACh have dual effects. For example, the ACh-M3 axis induces goblet cell metaplasia, extracellular matrix deposition, and bronchoconstriction; the CGRP-RAMP1 axis enhances Th2 and Th9 responses; and the SP-NK1R axis promotes the synthesis of chemokines in eosinophils, mast cells, and neutrophils. In contrast, the ACh-α7nAChR axis in ILC2 diminishes the synthesis of TNF-α, IL-1, and IL-6, attenuating lung inflammation whereas, VIP-VPAC1, N/OFQ-NOP axes cause bronchodilation and anti-inflammatory effects. Some NT/NP as 5-HT and NKA could be used as biomarkers to monitor asthma patients. In fact, the asthma treatment based on inhaled corticosteroids and anticholinergics blocks M3 and TRPV1 receptors. Moreover, the administration of experimental agents such as NK1R/NK2R antagonists and exogenous VIP decrease inflammatory mediators, suggesting that regulating the effects of NT/NP represents a potential novel approach for the treatment of asthma.

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“…Neuropeptides released from primary participate in immune modulation by several mechanisms. For example, substance P acting via neurokinin 1 receptors has a positive stimulatory effect on HSC activity and hematopoiesis [ 57 ], sustains the survival of activated T cells [ 58 ], stimulates macrophage production of proinflammatory mediators, and primes neutrophils to chemotaxis and migration [ 39 ]. In, contrast, CGRP acts as a negative regulator of innate immune responses and contributes to limiting tissue damage in inflammatory disorders.…”

Section: Immune Cells As Triggers and Targets Of Neuroimmune Interactmentioning

confidence: 99%

Peripheral neuroimmune interactions: selected review and some clinical implications

Shouman

Benarroch

2021

Clin Auton Res

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Purpose To provide a brief and focused review on peripheral neuroimmune interactions and their implications for some clinical disorders. Methods Narrative review of the literature including of English-language articles published between 1985 and 2021 using PubMed and MEDLINE. Results Many studies on experimental models and in vitro indicate that there are close interactions between the neural and immune systems. Processes from sensory afferents and autonomic efferents co-localize with immune cells and interact at discrete anatomical sites forming neuroimmune units. These neuroimmune interactions are bidirectional and mediated by a wide range of soluble factors including neuropeptides, classical neurotransmitters, cytokines, and other molecules that mediate complex cross-talk among nerves and immune cells. Small-diameter sensory afferents express a wide range of receptors that respond directly to tissue damage or pathogen signals and to chemokines, cytokines, or other molecules released from immune cells. Reciprocally, immune cells respond to neurotransmitters released from nociceptive and autonomic fibers. Neuroimmune interactions operate both at peripheral tissues and at the level of the central nervous system. Both centrally and peripherally, glial cells have a major active role in this bidirectional communication. Conclusions Peripheral neuroimmune interactions are complex and importantly contribute to the pathophysiology of several disorders, including skin, respiratory, and intestinal inflammatory disorders typically associated with pain and altered barrier function. These interactions may be relevant for persistence of symptoms in disorders associated with intense immune activation.

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

Cited by 26 publications

References 90 publications

Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

Neuroimmune Pathophysiology in Asthma

Peripheral neuroimmune interactions: selected review and some clinical implications

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