Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis

Dermatology and Therapy, Journal Year: 2022, Volume and Issue: 12(7), P. 1501 - 1533

Published: May 21, 2022

Type 2 immunity evolved to combat helminth infections by orchestrating a combined protective response of innate and adaptive immune cells promotion parasitic worm destruction or expulsion, wound repair, barrier function. Aberrant type responses are associated with allergic conditions characterized chronic tissue inflammation, including atopic dermatitis (AD) asthma. Signature cytokines include interleukin (IL)-4, IL-5, IL-9, IL-13, IL-31, mainly secreted from cells, as well IL-25, IL-33, thymic stromal lymphopoietin, particularly epithelial cells. IL-4 IL-13 key players mediating the prototypical response; initiates promotes differentiation proliferation naïve T-helper (Th) toward Th2 cell phenotype, whereas has pleiotropic effect on including, together IL-4, decreased Both implicated in B-cell isotype class switching generate immunoglobulin E, fibrosis, pruritus. regulator eosinophils, is responsible for eosinophil growth, differentiation, survival, mobilization. In AD, IL-31 sensory nerve sensitization itch, leading scratching that further exacerbates inflammation dysfunction. Various strategies have emerged suppress biologics targeting their receptors, Janus kinase inhibitors block intracellular cytokine signaling pathways. Here we review its role inflammatory diseases, current future therapies pathways, focus AD. INFOGRAPHIC.

Language: Английский

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Microneedle-mediated drug delivery for cutaneous diseases

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 17, 2022

Microneedles have garnered significant interest as transdermal drug delivery route owing to the advantages of nonselective loading capacity, minimal invasiveness, simple operation, and good biocompatibility. A number therapeutics can be loaded into microneedles, including hydrophilic hydrophobic small molecular drugs, macromolecular drugs (proteins, mRNA, peptides, vaccines) for treatment miscellaneous diseases. feature with special benefits cutaneous diseases direct skin. This review mainly introduces microneedles fabricated different technologies various diseases, such psoriasis, atopic dermatitis, skin soft tissue infection, superficial tumors, axillary hyperhidrosis, plantar warts.

Language: Английский

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NF-κB perturbation reveals unique immunomodulatory functions in Prx1 ⁺ fibroblasts that promote development of atopic dermatitis

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(630)

Published: Feb. 2, 2022

Skin is composed of diverse cell populations that cooperatively maintain homeostasis. Up-regulation the nuclear factor κB (NF-κB) pathway may lead to development chronic inflammatory disorders skin, but its role during early events remains unclear. Through analysis single-cell RNA sequencing data via iterative random forest leave one out prediction, an explainable artificial intelligence method, we identified immunoregulatory for a unique paired related homeobox-1 (Prx1) + fibroblast subpopulation. Disruption Ikkb –NF-κB under homeostatic conditions in these fibroblasts paradoxically induced skin inflammation due overexpression C-C motif chemokine ligand 11 (CCL11; or eotaxin-1) characterized by eosinophil infiltration and subsequent T H 2 immune response. Because phenotype resembled seen human atopic dermatitis (AD), examined AD samples found also overexpressed CCL11 perturbation primary dermal up-regulated CCL11. Monoclonal antibody treatment against was effective reducing eosinophilia mouse model. Together, murine model specimens point dysregulated Prx1 as previously unrecognized etiologic contribute pathogenesis suggest targeting be way treat AD-like lesions.

Language: Английский

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Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics

Clinical & Translational Immunology, Journal Year: 2022, Volume and Issue: 11(5)

Published: Jan. 1, 2022

Atopic dermatitis is a chronic inflammatory skin disease. Patients with atopic experience lesions associated intense itch and pain, which lead to sleep disturbance poor mental health quality of life. We review the molecular mechanisms underlying pain symptoms in discuss current clinical development treatments for moderate-to-severe dermatitis. The pathology includes aberrant immune activation involving significant cross-talk among neuronal cells. Exogenous endogenous triggers modulate stimulation mediators including cytokine/chemokine expression/release by cells, causes inflammation, barrier disruption, growth sensory neurons, pain. These complex interactions cell types are mediated primarily cytokines, but also involve chemokines, neurotransmitters, lipids, proteases, antimicrobial peptides, agonists ion channels or various G protein-coupled receptors. have cytokine profile characterised abnormal levels interleukins 4, 12, 13, 18, 22, 31 33; thymic stromal lymphopoietin; interferon gamma. Cytokine receptors mainly signal through Janus kinase/signal transducer activator transcription pathway. Among emerging novel therapeutics, several kinase inhibitors being developed topical systemic treatment because their potential expression release. changes gene that favourable effects on local release, probably other mediators, thus successfully modulating responsible

Language: Английский

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Microneedles-based drug delivery strategies: A breakthrough approach for the management of pain

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 155, P. 113717 - 113717

Published: Sept. 26, 2022

Pain is a personalized event or body alarm system that can limit patient's activities and lead to negative repercussions. The commercially available conventional treatment strategies like oral, parenteral, topical drug delivery systems for pain management are associated with side effects poor patient compliance. transdermal route eminent its painless distribution. Among system, microneedles (MNs) gaining attention their application at the deeper dermal layer because it bypasses major barrier of skin, easily accesses skin microcirculation, prevents damage blood vessels, be simply inserted into without utilizing any additional applicator devices. Hence, considered promising strategy high This review highlights recent advancements MNs in management. present work mainly emphasizes all case studies reported from past 10 years utilize containing therapeutics chronic pain-associated diseases rheumatoid arthritis, neuropathic pain, osteoarthritis, psoriatic atopic dermatitis. These have proven efficacious inflammation. also covered clinical trials, patents, future goals by using MNs.

Language: Английский

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