Mechanisms of skin autoimmunity: Cellular and soluble immune components of the skin

Guðjónsson, Jóhann E.; Kabashima, Kenji; Eyerich, Kilian

doi:10.1016/j.jaci.2020.05.009

Cited by 46 publications

(39 citation statements)

References 118 publications

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“…For example, the Th2/ILC2 or type 2 response is associated with "eczematous" skin conditions (such as AD, urticarial, etc.) and type 2 effector cytokines (IL-4, IL-5, IL-13, and IL-31) [44]. The most common itchy skin conditions are summarized in Table 2, on the basis of the clinical burden of pruritus and the underlying, selected immune-signatures.…”

Section: The Top Itchy Skin Diseasesmentioning

confidence: 99%

Pruritus as a Distinctive Feature of Type 2 Inflammation

et al. 2021

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Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients’ quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.

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Section: The Top Itchy Skin Diseasesmentioning

confidence: 99%

Pruritus as a Distinctive Feature of Type 2 Inflammation

et al. 2021

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“…Psoriasis and pityriasis rubra pilaris (PRP) have marked clinical and histological overlap, with both characterized by hyperplastic and hyperproliferative epidermis and varying degrees of dermal inflammatory infiltration (1)(2)(3). These two conditions share many molecular features such as skin barrier abnormalities (1,4,5), which has further led to the description of an intermediate psoriasis/familial PRP phenotype referred to "caspase recruitment domain family member 14 (CARD14)-associated papulosquamous eruption" (4), and possibly shared Interleukin (IL)-17 response (6,7).…”

Section: Introductionmentioning

confidence: 99%

Phospholipase A2 enzymes represent a shared pathogenic pathway in psoriasis and pityriasis rubra pilaris

Shao¹,

Chen²,

Swindell³

et al. 2021

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Altered epidermal differentiation along with increased keratinocyte proliferation, is a characteristic feature of psoriasis and pityriasis rubra pilaris (PRP). However, despite this large degree of overlapping clinical and histologic features, the molecular signatures these skin disorders share are unknown. Using global transcriptomic profiling we demonstrate that plaque psoriasis and PRP skin lesions have high overlap, with all differentially expressed genes in PRP relative to normal skin having complete overlap with those in psoriasis. The major common pathway shared between psoriasis and PRP involves the phospholipases: PLA2G2F, PLA2G4D, and PLA2G4E, which were found to be primarily expressed in the epidermis. Gene silencing targeting each of the three PLA2s led to reduction of immune responses and epidermal thickness both in vitro and in vivo in a mouse model of psoriasis, establishing their pro-inflammatory roles. Lipidomic analyses demonstrated that PLA2s affect mobilization of a phospholipid-eicosanoid pool, which is altered in psoriatic lesions and functions to promote immune responses in keratinocytes. Taken together, our results highlight the important role of PLA2 lipases as regulators of epidermal barrier homeostasis and inflammation, identify PLA2s as a shared pathogenic mechanism between PRP and psoriasis, and as potential novel therapeutic targets for both diseases.

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“…Immune cells are involved in innate and acquired immunity and provide resistance to foreign substances invading the body to maintain immune homeostasis in the body. If the balance of immunity is compromised, chronic inflammation or autoimmune diseases may occur [74,75]. Immune cells secrete EVs by inflammatory stimulation or external stimuli, and these EVs control inflammation by mediating interactions between immune cells [76].…”

Section: Extracellular Vesicles As Therapeutic Tools For Skin Diseasesmentioning

confidence: 99%

Extracellular Vesicles as Potential Theranostic Platforms for Skin Diseases and Aging

et al. 2021

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Extracellular vesicles (EVs), naturally secreted by cells, act as mediators for communication between cells. They are transported to the recipient cells along with cargoes such as nucleic acids, proteins, and lipids that reflect the changes occurring within the parent cells. Thus, EVs have been recognized as potential theranostic agents for diagnosis, treatment, and prognosis. In particular, the evidence accumulated to date suggests an important role of EVs in the initiation and progression of skin aging and various skin diseases, including psoriasis, systemic lupus erythematosus, vitiligo, and chronic wounds. This review highlights recent research that investigates the role of EVs and their potential as biomarkers and therapeutic agents for skin diseases and aging.

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Mechanisms of skin autoimmunity: Cellular and soluble immune components of the skin

Cited by 46 publications

References 118 publications

Pruritus as a Distinctive Feature of Type 2 Inflammation

Pruritus as a Distinctive Feature of Type 2 Inflammation

Phospholipase A2 enzymes represent a shared pathogenic pathway in psoriasis and pityriasis rubra pilaris

Extracellular Vesicles as Potential Theranostic Platforms for Skin Diseases and Aging

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