Neuronal Regulation of Immunity in the Skin and Lungs

Blake, Kimbria J.; Jiang, Xin; Chiu, Isaac M.

doi:10.1016/j.tins.2019.05.005

Cited by 74 publications

(62 citation statements)

References 87 publications

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“…Both TRPV1 and ALX/FPR2 are critical for the regulation of immunity and skin inflammation 1 , 48 , with TRPV1 playing a major role in psoriasiform skin inflammation and potentially in chronic itch 11 , 18 , 19 . Therefore, we asked whether RvD3 could reverse psoriasiform itch using a well-characterized preclinical mouse model of psoriasis.…”

Section: Resultsmentioning

confidence: 99%

“…The interaction between the immune and nervous system is a rapidly evolving topic in various skin diseases 1 - 3 , including psoriasis. Psoriasis affects 2-3% of the world's population, and is characterized by the presence of scaly skin plaques, thickened stratum corneum, infiltration and activation of inflammatory cells, arthritis and itch 4 .…”

Section: Introductionmentioning

confidence: 99%

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Resolvin D3 controls mouse and human TRPV1-positive neurons and preclinical progression of psoriasis

Lee

Tonello

et al. 2020

Theranostics

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Rationale: Psoriasis is a chronic inflammatory disease caused by a complex interplay between the immune and nervous systems with recurrent scaly skin plaques, thickened stratum corneum, infiltration and activation of inflammatory cells, and itch. Despite an increasing availability of immune therapies, they often have adverse effects, high costs, and dissociated effects on inflammation and itch. Activation of sensory neurons innervating the skin and TRPV1 (transient receptor potential vanilloid 1) are emerging as critical components in the pathogenesis of psoriasis, but little is known about their endogenous inhibitors. Recent studies have demonstrated that resolvins, endogenous lipid mediators derived from omega-3 fatty acids, are potent inhibitors of TRP channels and may offer new therapies for psoriasis without known adverse effects. Methods: We used behavioral, electrophysiological and biochemical approaches to investigate the therapeutic effects of resolvin D3 (RvD3), a novel family member of resolvins, in a preclinical model of psoriasis consisting of repeated topical applications of imiquimod (IMQ) to murine skin, which provokes inflammatory lesions that resemble human psoriasis. Results: We report that RvD3 specifically reduced TRPV1-dependent acute pain and itch in mice. Mechanistically, RvD3 inhibited capsaicin-induced TRPV1 currents in dissociated dorsal root ganglion (DRG) neurons via the N-formyl peptide receptor 2 (i.e. ALX/FPR2), a G-protein coupled receptor. Single systemic administration of RvD3 (2.8 mg/kg) reversed itch after IMQ, and repeated administration largely prevented the development of both psoriasiform itch and skin inflammation with concomitant decreased in calcitonin gene-related peptide (CGRP) expression in DRG neurons. Accordingly, specific knockdown of CGRP in DRG was sufficient to prevent both psoriasiform itch and skin inflammation similar to the effects following RvD3 administration. Finally, we elevated the translational potential of this study by showing that RvD3 significantly inhibited capsaicin-induced TRPV1 activity and CGRP release in human DRG neurons. Conclusions: Our findings demonstrate a novel role for RvD3 in regulating TRPV1/CGRP in mouse and human DRG neurons and identify RvD3 and its neuronal pathways as novel therapeutic targets to treat psoriasis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Resolvin D3 controls mouse and human TRPV1-positive neurons and preclinical progression of psoriasis

Lee

Tonello

et al. 2020

Theranostics

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“…Stress-response systems that can compromise barrier function range from the classical hypothalamic-pituitary-adrenal (HPA) axis via the (nor)adrenergic and cholinergic stress axis to neuropeptides and neurotrophins released in response to stress ( Blake et al, 2019 ; Slominski et al, 2012 ; Suarez et al, 2012 ). Barrier functions altered directly by stress include the decrease of epidermal hydration and increased transepidermal water loss due to the decrease of epidermal lipids and structural adhesion proteins, both of which allows viruses to trespass the barrier more easily.…”

Section: Lasting Psychosocial Stress Exposure Has a Negative Impact Omentioning

confidence: 99%

To stress or not to stress: Brain-behavior-immune interaction may weaken or promote the immune response to SARS-CoV-2

Peters

Schedlowski

Watzl

et al. 2021

Neurobiology of Stress

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“…The concept integrates well into the growing body of knowledge on neuroimmune cross-talk. Underlying mechanisms and molecular pathways were recently reviewed in detail elsewhere (65)(66)(67)(68).…”

Section: Functions In Homeostasismentioning

confidence: 99%

Origin and Differentiation of Nerve-Associated Macrophages

Kolter

Kierdorf

Henneke

2020

The Journal of Immunology

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The mature peripheral nervous system is a steady network structure yet shows remarkable regenerative properties. The interaction of peripheral nerves with myeloid cells has largely been investigated in the context of damage, following trauma or infection. Recently, specific macrophages dedicated to homeostatic peripheral nerves have come into focus. These macrophages are defined by tissue and nerve type, are seeded in part prenatally, and self-maintain via proliferation. Thus, they are markedly distinct from monocyte-derived macrophages invading after local disturbance of nerve integrity. The phenotypic and transcriptional adaptation of macrophages to the discrete nervous niche may exert axon guidance and nerve regeneration and thus contribute to the stability of the peripheral nervous network. Deciphering these conserved macrophage–nerve interactions offers new translational perspectives for chronic diseases of the peripheral nervous system, such as diabetic neuropathy and pain.

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Neuronal Regulation of Immunity in the Skin and Lungs

Cited by 74 publications

References 87 publications

Resolvin D3 controls mouse and human TRPV1-positive neurons and preclinical progression of psoriasis

Resolvin D3 controls mouse and human TRPV1-positive neurons and preclinical progression of psoriasis

To stress or not to stress: Brain-behavior-immune interaction may weaken or promote the immune response to SARS-CoV-2

Origin and Differentiation of Nerve-Associated Macrophages

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