Neuroimmune communication regulating pruritus in atopic dermatitis

Steinhoff, Martin; Faried, Ahmad; Pandey, Atul Kumar; Datsi, Angeliki; AlHammadi, Ayda; Al‐Khawaga, Sara; Al-Malki, Aysha; Meng, Jianghui; Alam, Majid; Buddenkotte, Joerg

doi:10.1016/j.jaci.2022.03.010

Cited by 65 publications

(63 citation statements)

References 382 publications

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“…The role of keratinocytes in sensation not only involves the intraepidermal, free nerve endings, but also communication with theses endings through chemical mediators [ 138 ]. While glutamate acts as a neuromediator, artemin has a neuroprotective role, as well as a role in sensation perception [ 139 ]. β-endorphin has a local effect for pain management [ 140 ].…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

El‐Serafi

El-Serafi

Steinvall

et al. 2022

IJMS

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Cell regenerative therapy is a modern solution for difficult-to-heal wounds. Keratinocytes, the most common cell type in the skin, are difficult to obtain without the creation of another wound. Stem cell differentiation towards keratinocytes is a challenging process, and it is difficult to reproduce in chemically defined media. Nevertheless, a co-culture of keratinocytes with stem cells usually achieves efficient differentiation. This systematic review aims to identify the secretions of normal human keratinocytes reported in the literature and correlate them with the differentiation process. An online search revealed 338 references, of which 100 met the selection criteria. A total of 80 different keratinocyte secretions were reported, which can be grouped mainly into cytokines, growth factors, and antimicrobial peptides. The growth-factor group mostly affects stem cell differentiation into keratinocytes, especially epidermal growth factor and members of the transforming growth factor family. Nevertheless, the reported secretions reflected the nature of the involved studies, as most of them focused on keratinocyte interaction with inflammation. This review highlights the secretory function of keratinocytes, as well as the need for intense investigation to characterize these secretions and evaluate their regenerative capacities.

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Section: Resultsmentioning

confidence: 99%

A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

El‐Serafi

El-Serafi

Steinvall

et al. 2022

IJMS

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“…Interaction between immune and barrier systems and, recently, that between immune and sensory nervous systems have been reported [ 27 , 28 , 29 , 36 , 37 , 38 , 39 , 40 , 41 ]. Therefore we analyzed gene expression of Th cytokines in SDS-treated earlobes to find that the SDS treatment induced upregulation of gene expression of Th2 (IL-4 but neither IL-5 nor IL-13) and Th17/Th22 (IL-17A, IL-17F, and IL-22) but not Th1 (IFN-γ) cytokines (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We do not exclude a possibility that modifications of the model to regulate expression of genes responsible to histamine production, histamine degradation, or H1 receptor signaling pathways may result in sensitivity to the H1-antihistamine treatment. Neurotransmitters other than histamine and receptors responsible in the present model are yet to be investigated [ 27 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Animal models of skin inflammation with H1 antihistamine-refractory itch would be useful for elucidation of mechanisms for refractory subtypes in itch-associated skin diseases such as atopic dermatitis, psoriasis, contact dermatitis, and so on [ 27 , 28 , 29 ]. In the present study, we examined induction of itch-associated inflammation in C57BL/6 mice on earlobe skin treatment of with 10% SDS for approximately 2 weeks and demonstrated that this strain showed H1-antihistamine-refractory itch.…”

Section: Introductionmentioning

confidence: 99%

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Skin Treatment with Detergent Induces Dermatitis with H1-Antihistamine-Refractory Itch and Upregulates IL-4 and Th17/Th22 Cytokine Gene Expression in C57BL/6 Mice

Masutani

Takai

Kamijo

et al. 2022

Int Arch Allergy Immunol

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Introduction: Repeated skin contact to detergents causes chronic irritant contact dermatitis (ICD) associated with itch sensation and eczema. However, the mechanisms of detergent-induced ICD are poorly understood. Here, we established a new murine model of detergent-induced ICD with H1-antihistamine-refractory itch. Methods: Ear skin of wild-type and mast cell-deficient mice on the C57BL/6 genetic background was treated with a detergent, sodium dodecyl/lauryl sulfate (SDS), daily for approximately 2 weeks with or without administration of an H1-antihistamine, fexofenadine. Skin inflammation, barrier dysfunction, and itching were analyzed. Quantitative PCR for earlobe gene expression and flow cytometry analysis for draining lymph node cells were conducted. Results: SDS treatment induced skin inflammation with ear swelling, increased transepidermal water loss, and hind-paw scratching behaviors in the wild-type and mast cell-deficient mice. The peak value of scratching bouts was retained for at least 48 h after the last SDS treatment. H1-antihistamine administration showed no or little reduction in the responses. SDS treatment upregulated gene expression for a Th2 cytokine IL-4 and Th17/Th22 cytokines, IL-17A, IL-17F, and IL-22, and increased cell numbers in draining lymph nodes of CD4+ T, CD8+ T, and γδT cells with enhanced expression of GATA3, RORγt, T-bet, or FOXP3 compared with untreated mice. Conclusions: The present study showed that SDS treatment of ear skin in C57BL/6 mice induces mast cell-independent skin inflammation with H1-antihistamine-refractory itch and suggested a possible Th cytokine- and/or lymphocyte-mediated regulation of the model. The model would be useful for elucidation of mechanisms for inflammation with H1-antihistamine-refractory itch in detergent-induced ICD.

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“…Moreover, the primary afferent nerves interact with the cutaneous cells by releasing neuroinflammatory mediators, which can modulate a range of physiological functions, including immunity, inflammation, sensory perception, and cell growth [ 66 ]. Dysregulation of the peripheral nerve fibers and neurotransmitters has been shown to contribute to the pathophysiology of inflammatory skin disorders, such as psoriasis and AD [ 67 , 68 ]. Recently, the morphological change of the peripheral nerve fibers [ 69 ] and the imbalanced expression of neuropeptides and neuroinflammatory mediators have been shown to have a pathogenic role in CNPG [ 70 ].…”

Section: Neuroinflammationmentioning

confidence: 99%

Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment

Wong

Yen

2022

IJMS

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Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic dermatitis, diabetes, and chronic renal diseases. The mechanisms of CNPG are complicated and involved the interaction of the cutaneous, immune, and nervous systems. Diverse immune cells, including eosinophils, neutrophils, T cells, macrophages, and mast cells infiltrated the lesional skin of CNPG, which initiated the inflammatory cytokines and pruritogens release. In addition, the interaction between the immune cells and activated peripheral sensory nerve fibers by neurotransmitters caused neuroinflammation in the skin and intractable itch. This itch-scratch vicious cycle of CNPG results in disease exacerbation. CNPG is difficult to treat with traditional therapies. Recently, great advances have been made in the pathophysiology of both inflammation and pruritus transmission in CNPG. In this review, we summarize the updated mechanisms and novel therapies for CNPG.

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Neuroimmune communication regulating pruritus in atopic dermatitis

Cited by 65 publications

References 382 publications

A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

Skin Treatment with Detergent Induces Dermatitis with H1-Antihistamine-Refractory Itch and Upregulates IL-4 and Th17/Th22 Cytokine Gene Expression in C57BL/6 Mice

Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment

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