Substance P Release by Sensory Neurons Triggers Dendritic Cell Migration and Initiates the Type-2 Immune Response to Allergens

Perner, Caroline; Flayer, Cameron H.; Zhu, Xueping; Aderhold, Pamela A.; Dewan, Zaynah N.A.; Voisin, Tiphaine; Camire, Ryan B.; Chow, Ohn A.; Chiu, Isaac M.; Sokol, Caroline L.

doi:10.1016/j.immuni.2020.10.001

Cited by 162 publications

(159 citation statements)

References 77 publications

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“…The skin’s barrier function is collectively carried out by several layers of tightly packed epithelial cells and sebaceous gland secretions forming an impermeable barrier. In addition, local immune cells and neural circuits perceive external threats via sensing of tissue damage, IgE-dependent mast cell activation and IL-31-dependent itch responses to control biting insects, remove ectoparasites, and limit contact with plant irritants (Bagci and Ruzicka, 2018; Olomski et al, 2020; Perner et al, 2020; Prussin and Metcalfe, 2003). Concomitantly, the skin’s continued exposure to pathogens and commensals must be managed to ensure that local invasion is prevented, tissue is repaired, and barrier function is quickly restored (Harrison et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The skin environment controls local dendritic cell differentiation and function through innate IL-13

Mayer

Lamiable

Hilligan

et al. 2021

Preprint

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The signals driving the adaptation of type-2 dendritic cells (DC2s) to diverse peripheral environments are not well understood. We show that the development of CD11blow migratory DC2s, a DC2 population unique to the dermis, requires STAT6- and KLF4-dependent IL-13 signaling, whereas DC2s in lung and small intestine are STAT6-independent. Dermal IL-13 is mostly derived from innate lymphoid cells expressing a resting ICOS+ KLRG1-ST2-phenotype. Analysis of public datasets indicates that human skin DC2s also express an IL-4/IL-13 gene signature compared to blood or spleen, suggesting a similar developmental pathway in mice and humans. In the absence of IL-13 signaling, dermal DC2s are stable in number but remain CD11bhi and show defective activation in response to allergen with diminished ability to support IL-4+ GATA3+ Th development, whereas anti-fungal IL-17+ RORγt+ responses are increased. Thus, steady-state IL-13 fosters a non-inflammatory and pro-allergic environment in healthy skin via conditioning of local DC2s.

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Section: Introductionmentioning

confidence: 99%

The skin environment controls local dendritic cell differentiation and function through innate IL-13

Mayer

Lamiable

Hilligan

et al. 2021

Preprint

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“…When we examined cumulative distributions of the peak response amplitudes for responses classified as positive or negative (Figure 2b), we observed overlap between the two distributions; however manual qualitative spot checks of responses classified as positive and negative within the low amplitude range ( Figure 2c) revealed striking differences in the dynamics of the calcium response, with the negative responses visually indicative of stimulus artifacts resulting from liquid injection. Notably, use of a fixed threshold, as is currently the standard approach to such analyses (Blanchard et al, 2015;Perner et al, 2020), which would have classified these artifacts as positive responses, and thus would have resulted in increased false positive responses.…”

Section: Resultsmentioning

confidence: 99%

A high-content platform for physiological profiling and unbiased classification of individual neurons

Dubreuil

Chiang

Zhu

et al. 2021

Preprint

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High-throughput physiological assays often lose single cell resolution, precluding subtype-specific analyses of neuronal activation mechanism and drug effects. Here, we demonstrate APPOINT, Automated Physiological Phenotyping Of Individual Neuronal Types. This physiological assay platform combines calcium imaging, robotic liquid handling, and automated analysis to generate physiological activation profiles of single neurons at a large scale. Using unbiased techniques, we quantify responses to multiple sequential stimuli, enabling subgroup identification by physiology and probing of distinct mechanisms of neuronal activation within subgroups. Using APPOINT, we quantify primary sensory neuron activation by metabotropic receptor agonists and identify potential contributors to pain signaling. Furthermore, we expand the role of neuroimmune interactions by showing that human serum can directly activate sensory neurons, elucidating a new potential pain mechanism. Finally, we apply APPOINT to develop a high-throughput, all-optical approach for quantification of activation threshold and pharmacologically separate the contributions of distinct ion channel subsets to optical activation.

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“…Neurons involve various skin physiological and pathological functions, leading to the development of various skin diseases [ 29 ]. Nerves also exert various cells to promote physiological and pathological functions [ 30 ]. CADM1 develops synaptic adhesion which drives synapse assembly [ 7 ].…”

Section: The Role Of Cadm1 In Cell Typesmentioning

confidence: 99%

The Role of Cell Adhesion Molecule 1 (CADM1) in Cutaneous Malignancies

Sawada

Mashima

Saito‐Sasaki

et al. 2020

IJMS

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Cell adhesion ability is one of the components to establish cell organization and shows a great contribution to human body construction consisting of various types of cells mixture to orchestrate tissue specific function. The cell adhesion molecule 1 (CADM1) is a molecule of cell adhesion with multiple functions and has been identified as a tumor suppressor gene. CADM1 has multifunctions on the pathogenesis of malignancies, and other normal cells such as immune cells. However, little is known about the function of CADM1 on cutaneous cells and cutaneous malignancies. CADM1 plays an important role in connecting cells with each other, contacting cells to deliver their signal, and acting as a scaffolding molecule for other immune cells to develop their immune responses. A limited number of studies reveal the contribution of CADM1 on the development of cutaneous malignancies. Solid cutaneous malignancies, such as cutaneous squamous cell carcinoma and malignant melanoma, reduce their CADM1 expression to promote the invasion and metastasis of the tumor. On the contrary to these cutaneous solid tumors except for Merkel cell carcinoma, cutaneous lymphomas, such as adult-T cell leukemia/lymphoma, mycosis fungoides, and Sézary syndrome, increase their CADM1 expression for the development of tumor environment. Based on the role of CADM1 in the etiology of tumor development, the theory of CADM1 contribution will desirably be applied to skin tumors according to other organ malignancies, however, the characteristics of skin as a multicomponent peripheral organ should be kept in mind to conclude their prognoses.

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Substance P Release by Sensory Neurons Triggers Dendritic Cell Migration and Initiates the Type-2 Immune Response to Allergens

Cited by 162 publications

References 77 publications

The skin environment controls local dendritic cell differentiation and function through innate IL-13

The skin environment controls local dendritic cell differentiation and function through innate IL-13

A high-content platform for physiological profiling and unbiased classification of individual neurons

The Role of Cell Adhesion Molecule 1 (CADM1) in Cutaneous Malignancies

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