Complement Activation in Inflammatory Skin Diseases

Giang, Jenny; Seelen, Marc A.; Doorn, Martijn van; Rißmann, Robert; Prens, Errol P.; Damman, Jeffrey

doi:10.3389/fimmu.2018.00639

Cited by 95 publications

(87 citation statements)

References 134 publications

(144 reference statements)

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“…However, these markers can often be used to follow individual patients if the baseline values are known or can be anticipated e.g. as in trauma and shock ( 7 ), sepsis ( 8 ), in neurological diseases such as myasthenia gravis ( 9 ), in ophthalmic diseases such as age-related macular degeneration, (AMD) ( 10 ), bullous pemphigoid ( 11 ), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis ( 12 ) etc. They can also be used for research purposes.…”

Section: The Complement Systemmentioning

confidence: 99%

Interpretation of Serological Complement Biomarkers in Disease

et al. 2018

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Complement system aberrations have been identified as pathophysiological mechanisms in a number of diseases and pathological conditions either directly or indirectly. Examples of such conditions include infections, inflammation, autoimmune disease, as well as allogeneic and xenogenic transplantation. Both prospective and retrospective studies have demonstrated significant complement-related differences between patient groups and controls. However, due to the low degree of specificity and sensitivity of some of the assays used, it is not always possible to make predictions regarding the complement status of individual patients. Today, there are three main indications for determination of a patient's complement status: (1) complement deficiencies (acquired or inherited); (2) disorders with aberrant complement activation; and (3) C1 inhibitor deficiencies (acquired or inherited). An additional indication is to monitor patients on complement-regulating drugs, an indication which may be expected to increase in the near future since there is now a number of such drugs either under development, already in clinical trials or in clinical use. Available techniques to study complement include quantification of: (1) individual components; (2) activation products, (3) function, and (4) autoantibodies to complement proteins. In this review, we summarize the appropriate indications, techniques, and interpretations of basic serological complement analyses, exemplified by a number of clinical disorders.

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Section: The Complement Systemmentioning

confidence: 99%

Interpretation of Serological Complement Biomarkers in Disease

et al. 2018

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“…T cell activation is thought to be initiated and driven by DCs which produce various proinflammatory cytokines, including IL-6 and IL-23, further driving Th17 cell-mediated inflammation [2]. The following histological features of psoriasis are generally accepted: a greatly thickened epidermis with elongated rete ridges into the dermis, an increased number of prominent blood vessels in the papillary dermis, and the presence of a collection of neutrophils in the cornified layer known as a Munro's microabscess (MM) [3]. Interestingly, there are clinical reports that psoriasis is worsened by psychosocial stress [4].…”

Section: Introductionmentioning

confidence: 99%

TRPV1 mediates inflammation and hyperplasia in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice

Zhou

Follansbee

et al. 2018

Journal of Dermatological Science

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A B S T R A C TBackground: Transient Receptor Potential Vanilloid 1 (TRPV1) is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in psoriasiform dermal inflammation is poorly understood. Objective: To investigate the function of TRPV1 in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice. Methods: Following daily treatment of topical IMQ cream for consecutive 5 days in C57BL/6 wide-type (WT) and TRPV1 gene knockout (KO) mice, we assessed the psoriasis severity index (PSI) scores, transepidermal water loss (TEWL), dermal inflammatory infiltrates, as well as gene expression levels for psoriasis related genes in mouse skin lesions. Results: Compared with WT mice, the clinical and TEWL scores, the extent of skin hyperplasia, the area of Munro microabscesses (MM) and angiogenesis of psoriasis were all significantly decreased in TRPV1 KO mice triggered with IMQ, suggesting a reduction in skin inflammation and barrier defects. In addition, the infiltration of CD45 + leukocytes, mast cells as well as CD3 + T cells was all reduced in the IMQ-treated skin of TRPV1 KO mice. Quantitative Real-time PCR (RT-qPCR) revealed that expression levels of IL-1β, IL-6, IL-23, S100A8 were decreased while IL-10 was increased in TRPV1 KO mice. Conclusions: In summary, key markers of psoriatic inflammation and epidermal hyperplasia are reduced in TRPV1 KO mice, indicating the involvement of TRPV1 in the psoriasiform inflammation and suggesting its potential as a therapeutic target.

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“…The complement system is an instrumental part of the innate immune system, contributing substantially to tissue homeostasis. Emerging evidence pointed out that activation of the complement system exhibits an essential role in skin defense against microbial infection but also mediates inflammation and tissue injury . Genetic deficiencies or abnormal activation of complement components or regulators are often related to certain skin diseases .…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence pointed out that activation of the complement system exhibits an essential role in skin defense against microbial infection but also mediates inflammation and tissue injury . Genetic deficiencies or abnormal activation of complement components or regulators are often related to certain skin diseases . MBL is an essential component which initiates the complement cascades via lectin pathway .…”

Section: Discussionmentioning

confidence: 99%

Mannan‐binding lectin promotes keratinocyte to produce CXCL1 and enhances neutrophil infiltration at the early stages of psoriasis

Zeng

Chen

et al. 2019

Experimental Dermatology

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Psoriasis is a chronic, relapsing inflammatory skin disorder. Numerous experimental evidence and therapeutic evidence have shown that the innate immune response is critical for the pathogenesis and development of psoriasis. Mannan‐binding lectin (MBL), a prototypic pattern recognition molecule of the innate immune system, plays an essential role in the host defense against certain infections and also appears to be a major regulator of inflammation. In this study, we investigated the function of MBL on the course of experimental murine imiquimod (IMQ)‐induced psoriasis. Our data showed that MBL‐deficient (MBL−/−) mice exhibited attenuated skin damage characterized by greatly decreased erythema compared with wild‐type control mice during the early stages of IMQ‐induced psoriasis‐like skin inflammation. The reduced skin inflammation in MBL−/− mice was associated with the decreased infiltration of neutrophils. Furthermore, we have determined that MBL deficiency limited the chemokine CXCL1 production from skin keratinocytes upon IMQ stimulation, which might be responsible for the impaired skin recruitment of neutrophils. Additionally, we have provided the data that MBL protein promotes the IMQ‐induced expression of CXCL1 and activation of MAPK/NF‐κB signalling pathway in human keratinocyte HaCaT cells in vitro. In summary, our study revealed an unexpected role of MBL on keratinocyte function in skin, thus offering a new insight into the pathogenic mechanisms of psoriasis.

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Complement Activation in Inflammatory Skin Diseases

Cited by 95 publications

References 134 publications

Interpretation of Serological Complement Biomarkers in Disease

Interpretation of Serological Complement Biomarkers in Disease

TRPV1 mediates inflammation and hyperplasia in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice

Mannan‐binding lectin promotes keratinocyte to produce CXCL1 and enhances neutrophil infiltration at the early stages of psoriasis

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