Binding and in vitro modulation of human epidermal Langerhans cell functions by substance P

Staniek, V; Miséry, Laurent; Pèguet‐Navarro, Josette; Abello, Jacques; Doutremepuich, Jean-Daniel; Claudy, A; Schmitt, Daniel

doi:10.1007/s004030050194

Cited by 46 publications

(29 citation statements)

References 32 publications

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“…Importantly, our data demonstrate for the first time constitutive expression of the NK1R by murine LCs, indicating that signaling LCs directly via the NK1R may affect their APC function and ability to express transgenes. Accordingly, neuropeptides such as SP and calcitonin gene-related peptide, secreted by cutaneous ␦ fibers, exert important immune-modulation of LCs (13) and previous reports (23,64) have shown that the NK1R agonist down-regulates the migratory function of LCs. However, our results clearly indicate that the NK1R agonist triggers a massive and rapid LC mobilization of the epidermis.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Signaling through the Neurokinin 1 Receptor Favors Transgene Expression by Langerhans Cells and Promotes the Generation of Th1- and Tc1-Biased Immune Responses

Mathers¹,

Tckacheva²,

Janelsins³

et al. 2007

The Journal of Immunology

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The proinflammatory capacities of the skin and the presence of high numbers of resident dendritic cells (DCs) constitute an ideal microenvironment for successful immunizations. Regardless of the ability of DCs to respond to local inflammatory signals in an immunostimulatory fashion, the immune functions of skin-resident DCs remain controversial, and epidermal Langerhans cells (LCs) have been referred to recently as anti-inflammatory/protolerogenic APCs. Substance P (SP), released by skin nerve fibers, is a potent proinflammatory neuropeptide that favors development of skin-associated cellular immunity. SP exerts its proinflammatory functions by binding with high affinity to the neurokinin 1 receptor (NK1R). In this study, we tested whether signaling skin cells via the NK1R promotes humoral and cellular immunity during skin genetic immunizations. We used the gene gun to deliver transgenic (tg) Ag to the skin of C57BL/6 mice and the selective NK1R agonist [Sar9Met (O2) 11]-SP as a potential proinflammatory Th1-biasing adjuvant. Our strategy expressed tg Ag exclusively in the epidermis and induced a preferential migration of activated LCs to skin-draining lymph nodes. Local administration of the NK1R agonist during skin genetic immunizations increased significantly the expression of tg Ag by a mechanism involving the translocation of NF-κB into the nuclei of cutaneous DCs homing to skin-draining lymph nodes. Importantly, our immunization approach resulted in Th1 and T cytotoxic (CTL)-1 bias of effector T cells that supported cellular and Ab-mediated immune responses. We demonstrate that signaling skin cells via the NK1R provides the adjuvant effect which favors the immunostimulatory functions of LCs.

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Section: Discussionmentioning

confidence: 99%

In Vivo Signaling through the Neurokinin 1 Receptor Favors Transgene Expression by Langerhans Cells and Promotes the Generation of Th1- and Tc1-Biased Immune Responses

Mathers¹,

Tckacheva²,

Janelsins³

et al. 2007

The Journal of Immunology

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“…12 No entanto, deve-se mencionar que isso é uma generalização e que há resultados de efeitos inibitórios da SP em altas concentrações sobre a resposta de células T em modelos de HTT in vitro que podem ser de alguma relevância in vivo. 132 O CGRP, por sua vez, tem sido intensamente estudado em sua capacidade de inibir as reações de HTT por suprimir a apresentação de antígeno por células de Langerhans (vide acima, na descrição do peptídeo). Na pele, há fibras imunorreativas para o CGRP em íntimo contato com células de Langerhans.…”

Section: Reações De Hipersensibilidadeunclassified

Neuropeptídeos na pele

Kalil-Gaspar

2003

An. Bras. Dermatol.

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Resumo: Há evidências crescentes de que a inervação cutânea é capaz de modular uma variedade de fenômenos cutâneos agudos e crônicos, interagindo com as células da pele e seus componentes imunes. Essa forma de sinalização local entre tecido nervoso e tecido cutâneo ocorre especialmente por meio dos neuropeptídeos, uma numerosa família de neurotransmissores de natureza química comum e nomenclatura heterogênea presentes em todo o sistema nervoso e secretados pelas fibras nervosas cutâneas. São alvo desta revisão os neuropeptídeos substância P (SP), o peptídeo relacionado ao gene da calcitonina (CGRP), o peptídeo vasoativo intestinal (VIP), o peptídeo ativador da adenilato-ciclase pituitária (PACAP), o neuropeptídeo Y (NPY) e a somatostatina ( SOM). Serão discutidas suas ações sobre as células da pele e sistema imune, bem como estudos recentes que sugerem a participação dos neuropeptídeos nas respostas inflamatórias cutâneas, nas reações de hipersensibilidade e em dermatoses humanas, notadamente na psoríase, dermatite atópica, hanseníase e alopecia. Palavras-chave: alopecia; dermatite atópica; fatores de crescimento neural; hanseníase; hipersensibilidade; neuropeptídeos; pele; psoríase. Summary: There is increasing evidence that cutaneous nerve fibers play a modulatory role in a variety of acute and chronic skin processes. Local interactions between skin cells, skin immune components and neuronal tissues occur specially through neuropeptides, a large family of chemically-related neurotransmitters exhibiting a heterogeneous nomenclature. Neuropeptides are ubiquitous in central and peripheral nervous systems, being directly released in skin by cutaneous nerve fibers. This review is focused on the actions of substance P (SP), calcitonin gene-related peptide (CGRP), vasointestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y (NPY) and somatostatin (SOM). Neuropeptide-related functions on skin and immune cells are also discussed, as well as recent findings implicating nerve fibers in cutaneous inflammatory Artigo de Revisão / Review Article INTRODUÇÃOAs vias de interação entre as células imunes e as células da pele constituem base teórica comum na dermatologia moderna. A proposta desta revisão é abordar estudos que mostram que a inervação da pele possui um variado repertório de sinalização local com o tecido cutâneo e as células imunes, revelando funções que excedem seu histó-rico papel sensorial e complementam o conhecimento atual da fisiologia cutânea e etiopatogenia das doenças dermatológicas. A concepção de que fibras nervosas cutâneas, célu-las imunes e células da pele possuem formas de interação recíprocas compõe o que alguns autores têm denominado sistema neuroimunocutâneo. INTRODUCTION A common basic theory in modern dermatology relates to the interaction between immune cells and the cells of the

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“…This action most often happens via receptors coupled with protein G. Neuromediators modulate functions of all cutaneous cell types: endothelial cells, muscle cells, eccrine or apocrine glandular cells, immune cells, fibroblasts, epidermal cells. In a mixed lympho-epidermal reaction in humans, substance P [93] can inhibit antigen presentation to lymphocytes, though NK1-type receptors on both Langerhans cells and T lymphocytes. In a similar model on mice, CGRP inhibits the presentation of antigens [43].…”

Section: Functional Connectionsmentioning

confidence: 99%

“…Langerhans cells produce pro-opiomelanocortin (precursor to MSH, ACTH and β-endorphin) [13]. Through receptors on their surface, the function of Langerhans cells is modulated by neuromediators: CGRP [43], substance P [93], GRP [94], and αMSH [87]. In atopic dermatitis, Langerhans cells seem to express the receptor for neuropeptide Y [76].…”

Section: Langerhans Cellsmentioning

confidence: 99%

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Are Biochemical Mediators the Missing Link between Psychosomatics and Dermatology?

Miséry¹

2001

Dermatol Psychosom

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There are numerous evidences that point to a close association between psychosomatics and dermatology. The course of dermatological disorders is more or less influenced by psychological factors and stress events, whereby the process depends on the patient, on the disease and on the particular circumstances in the life of the patient. Links between psyche and skin appear to be very intimate, especially when the immune system is involved in skin diseases. Many psychogenic concepts are able to explain why the onset of cutaneous lesions can be triggered by a psychological disorder and/or a stress life events. These theories do not exclude that there is a biochemical substratum for psychosomatics in dermatology. Indeed, the influence of psyche on skin implies that there are chemical factors that translate an emotion or stress to a cutaneous lesion: these factors are neurotransmitters and hormones. These mediators can be produced directly in the skin by nerve fibers, but also by other cells and distributed by the blood flow. They are able to modulate properties of the skin through receptors on the cell membrane. Amounts of mediators and levels of expression of their receptors can be modified in response to a stress. Hence, an imbalance in the homeostasis of mediators and receptors could induce an imbalance between many neurotransmitters and hormones, influencing skin cells to the point of disease, given a particular genetic susceptibility.

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Binding and in vitro modulation of human epidermal Langerhans cell functions by substance P

Cited by 46 publications

References 32 publications

In Vivo Signaling through the Neurokinin 1 Receptor Favors Transgene Expression by Langerhans Cells and Promotes the Generation of Th1- and Tc1-Biased Immune Responses

In Vivo Signaling through the Neurokinin 1 Receptor Favors Transgene Expression by Langerhans Cells and Promotes the Generation of Th1- and Tc1-Biased Immune Responses

Neuropeptídeos na pele

Are Biochemical Mediators the Missing Link between Psychosomatics and Dermatology?

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