Sensory Nerves Regulate Transcriptional Dynamics of Lymph Node Cells

Wang, Peter L.; Czepielewski, Rafael S.; Randolph, Gwendalyn J.

doi:10.1016/j.it.2021.01.008

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…DSCH involves the exchange of immune cells back and forth between skin-challenged sites and the nearby lymph nodes. The mobilization of specific memory T cells from the lymph nodes to the skin during DSCH is favored by the substance P released from sensory neurons [ 40 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. To evaluate whether the exacerbation of DSCH in BE mice indeed involved immune memory, we assessed whether ear swelling could be prevented or attenuated in S and BE mice after antagonizing the actions of substance P in the auricular lymph node.…”

Section: Methodsmentioning

confidence: 99%

Looking beyond Self-Protection: The Eyes Instruct Systemic Immune Tolerance Early in Life

Villafán,

Gutiérrez-Ospina

2023

Brain Sciences

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The eyes provide themselves with immune tolerance. Frequent skin inflammatory diseases in young blind people suggest, nonetheless, that the eyes instruct a systemic immune tolerance that benefits the whole body. We tested this premise by using delayed skin contact hypersensitivity (DSCH) as a tool to compare the inflammatory response developed by sighted (S) and birth-enucleated (BE) mice against oxazolone or dinitrofluorobenzene at the ages of 10, 30 and 60 days of life. Adult mice enucleated (AE) at 60 days of age were also assessed when they reached 120 days of life. BE mice displayed exacerbated DSCH at 60 but not at 10 or 30 days of age. AE mice, in contrast, show no exacerbated DSCH. Skin inflammation in 60-day-old BE mice was hapten exclusive and supported by distinct CD8+ lymphocytes. The number of intraepidermal T lymphocytes and migrating Langerhans cells was, however, similar between S and BE mice by the age of 60 days. Our observations support the idea that the eyes instruct systemic immune tolerance that benefits organs outside the eyes from an early age. The higher prevalence of inflammatory skin disorders reported in young people might then reflect reduced immune tolerance associated with the impaired functional morphology of the eyes.

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Section: Methodsmentioning

confidence: 99%

Looking beyond Self-Protection: The Eyes Instruct Systemic Immune Tolerance Early in Life

Villafán,

Gutiérrez-Ospina

2023

Brain Sciences

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“…In other tissues, CGRP and substance P released by peptidergic fibers within the skin may be transported within the draining lymph to affect lymphatic vessel function [ 202 ]. Sensory nerves can regulate transcriptional dynamics in lymphatic tissue and regulate immune function [ 203 , 204 ]. In systemic lymphedema, CGRP ameliorates lymphedema by enhancing lymphatic capillary formation and regulates macrophage recruitment [ 205 ].…”

Section: Pulmonary Fibrosis and Fluid Clearancementioning

confidence: 99%

Role of Sensory Nerves in Pulmonary Fibrosis

Norton

2024

IJMS

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Pulmonary fibrosis results from the deposition and proliferation of extracellular matrix components in the lungs. Despite being an airway disorder, pulmonary fibrosis also has notable effects on the pulmonary vasculature, with the development and severity of pulmonary hypertension tied closely to patient mortality. Furthermore, the anatomical proximity of blood vessels, the alveolar epithelium, lymphatic tissue, and airway spaces highlights the need to identify shared pathogenic mechanisms and pleiotropic signaling across various cell types. Sensory nerves and their transmitters have a variety of effects on the various cell types within the lungs; however, their effects on many cell types and functions during pulmonary fibrosis have not yet been investigated. This review highlights the importance of gaining a new understanding of sensory nerve function in the context of pulmonary fibrosis as a potential tool to limit airway and vascular dysfunction.

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“…

As secondary lymphoid organs, the spleen and lymph node represent important hubs for both innate and adaptive immunity 1,2 . Neuroanatomical and tracing data, largely derived from rodents, suggest that lymph nodes contain sensory and sympathetic innervation 3,4 , whereas the spleen contains postganglionic sympathetic innervation 5 , with conflicting views regarding the existence of cholinergic or vagal innervation 6 . Herein, we map the neuronal, vascular, and sinus cell networks from human spleen and lymph node using highly multiplexed CODEX (CO-Detection by indEXing) and 3D light sheet microscopy of cleared tissues.

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mentioning

confidence: 99%

Immune, endothelial and neuronal network map in human lymph node and spleen

Currlin

Nick

Jorgensen

et al. 2021

Preprint

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As secondary lymphoid organs, the spleen and lymph node represent important hubs for both innate and adaptive immunity. Neuroanatomical and tracing data, largely derived from rodents, suggest that lymph nodes contain sensory and sympathetic innervation, whereas the spleen contains postganglionic sympathetic innervation, with conflicting views regarding the existence of cholinergic or vagal innervation. Herein, we map the neuronal, vascular, and sinus cell networks from human spleen and lymph node using highly multiplexed CODEX (CO-Detection by indEXing) and 3D light sheet microscopy of cleared tissues. These data demonstrate striking delineation of two distinct layers within the lymph node subcapsular sinus-the ceiling defined by Podoplanin expression and floor by LYVE1, which overlays the lymph node follicles. Within the lymph node interior, we observed a mesh-like vessel network innervated with GAP43 and beta3-tubulin. Dense perivascular innervation occurred in both tissues, including a subset of axonal processes expressing choline acetyl transferase (ChAT). Four neuronal markers (ChAT, PGP9.5, tyrosine hydroxylase, and beta3-tubulin) localized to the arterial tunica externa suggest expression in the nervi vasorum while GAP43 was expressed within the internal elastic membrane of arteries. These data represent highly novel 3D visualization of perivascular and periductal autonomic innervation within these two key human organs.

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Sensory Nerves Regulate Transcriptional Dynamics of Lymph Node Cells

Cited by 4 publications

References 10 publications

Looking beyond Self-Protection: The Eyes Instruct Systemic Immune Tolerance Early in Life

Looking beyond Self-Protection: The Eyes Instruct Systemic Immune Tolerance Early in Life

Role of Sensory Nerves in Pulmonary Fibrosis

Immune, endothelial and neuronal network map in human lymph node and spleen

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