Skin Injury Activates a Rapid TRPV1-Dependent Antiviral Protein Response

Lei, Vivian; Handfield, Chelsea; Kwock, J.; Kirchner, Stephen J.; Lee, Min Jin; Coates, Margaret; Wang, Kaiyuan; Han, Qingjian; Wang, Zilong; Powers, Jennifer G.; Wolfe, Sarah A.; Corcoran, David L.; Fanelli, Brian; Dadlani, Manoj; Ji, Ru-Rong; Zhang, Jennifer; MacLeod, Amanda S.

doi:10.1016/j.jid.2021.11.041

Cited by 9 publications

(5 citation statements)

References 79 publications

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“…CGRP release is required for this TRPV1 + neuron-induced type-17 inflammation. Another recent study suggested that, following skin injury in mice, TRPV1 + neurons may enhance the antiviral host response by inducing the production of proteins with antiviral properties, such as Oas2, Oasl2, and Isg15 [29]. These studies show that the contribution of skin sensory neurons to host defense is highly context-dependent.…”

Section: Neuroimmune Interactions and The Host Response To Pathogensmentioning

confidence: 74%

Neuroimmune crosstalk in the skin: a delicate balance governing inflammatory processes

Roger

Reynders²,

Hoeffel³

et al. 2022

Current Opinion in Immunology

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Section: Neuroimmune Interactions and The Host Response To Pathogensmentioning

confidence: 74%

Neuroimmune crosstalk in the skin: a delicate balance governing inflammatory processes

Roger

Reynders²,

Hoeffel³

et al. 2022

Current Opinion in Immunology

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“…The skin is the interface between body and environmental factors, and it acts as the first line of defense against many insults, including microbes. 36,65 It plays a fundamental role in innate antimicrobial host immunity. 66 Moreover, with the aging process of the skin, the three layers of skin (epidermis, dermis, and hypodermis) undergo degenerative changes, and alterations of the dermis are the most obvious.…”

Section: Discussionmentioning

confidence: 99%

“…This entry of calcium reduces inflammatory responses, thereby decreasing harmful cutaneous conditions. More recently, Lei et al 36 reported that TRPV1 signaling ensures skin antiviral competence during wound healing by an unknown mechanism of skin injury activating a TRPV1-mediated innate antiviral immune response. Other TRP channels have been reported to be expressed in nonneuronal cells as well such as TRPM4 in focal adhesions of fibroblasts, 37 TRPV2 in retinal vascular smooth muscle cells, 38 TRPV4 in endothelial cells of the blood brain barrier.…”

Section: Introductionmentioning

confidence: 99%

Relation Between Reactive Oxygen Species Production and Transient Receptor Potential Vanilloid1 Expression in Human Skin During Aging

Favero,

Gianò,

Franco

et al. 2024

J Histochem Cytochem.

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Skin sensitivity and impaired epidermal barrier function are associated with aging and are at least partly due to increased production of reactive oxygen species (ROS). Transient receptor potential vanilloid1 (TRPV1) is expressed in keratinocytes, fibroblasts, mast cells, and endothelial cells in skin. We investigated in skin biopsies of adult and elderly donors whether TRPV1 expression is involved in the skin aging process. We found that aging skin showed a strongly reduced epidermal thickness, strongly increased oxidative stress, protease expression, and mast cell degranulation and strongly increased TRPV1 expression both in epidermis and dermis. Based on our findings, the aging-related changes observed in the epidermis of the skin level are associated with increased ROS production, and hypothesized alterations in TRPV1 expression are mechanistically linked to this process.

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“…Through a yet-to-be defined mechanism, activation of cutaneous nociceptors was sufficient to induce IL-27 expression by dermal CD301b + cellsa heterogenous group of myeloid cells that includes cDC2s as well as monocyte-derived cellswhich, in turn, induced expression of anti-viral peptides in keratinocytes. Indeed, skin explants from TRPV-1 deficient mice were more susceptible to HSV infection than those from WT controls (146). Furthermore, DCs isolated from skin-draining lymph nodes of HSV-infected nociceptor-deficient animals were unable to efficiently prime cognate T-cells.…”

Section: Dendritic Cellsmentioning

confidence: 99%

Control of myeloid cell functions by nociceptors

et al. 2023

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The immune system has evolved to protect the host from infectious agents, parasites, and tumor growth, and to ensure the maintenance of homeostasis. Similarly, the primary function of the somatosensory branch of the peripheral nervous system is to collect and interpret sensory information about the environment, allowing the organism to react to or avoid situations that could otherwise have deleterious effects. Consequently, a teleological argument can be made that it is of advantage for the two systems to cooperate and form an “integrated defense system” that benefits from the unique strengths of both subsystems. Indeed, nociceptors, sensory neurons that detect noxious stimuli and elicit the sensation of pain or itch, exhibit potent immunomodulatory capabilities. Depending on the context and the cellular identity of their communication partners, nociceptors can play both pro- or anti-inflammatory roles, promote tissue repair or aggravate inflammatory damage, improve resistance to pathogens or impair their clearance. In light of such variability, it is not surprising that the full extent of interactions between nociceptors and the immune system remains to be established. Nonetheless, the field of peripheral neuroimmunology is advancing at a rapid pace, and general rules that appear to govern the outcomes of such neuroimmune interactions are beginning to emerge. Thus, in this review, we summarize our current understanding of the interaction between nociceptors and, specifically, the myeloid cells of the innate immune system, while pointing out some of the outstanding questions and unresolved controversies in the field. We focus on such interactions within the densely innervated barrier tissues, which can serve as points of entry for infectious agents and, where known, highlight the molecular mechanisms underlying these interactions.

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Skin Injury Activates a Rapid TRPV1-Dependent Antiviral Protein Response

Cited by 9 publications

References 79 publications

Neuroimmune crosstalk in the skin: a delicate balance governing inflammatory processes

Neuroimmune crosstalk in the skin: a delicate balance governing inflammatory processes

Relation Between Reactive Oxygen Species Production and Transient Receptor Potential Vanilloid1 Expression in Human Skin During Aging

Control of myeloid cell functions by nociceptors

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