Pattern Recognition Receptors in Immune Disorders Affecting the Skin

Koning, Heleen D. de; Simon, Anna; Zeeuwen, Patrick L.J.M.; Schalkwijk, Joost

doi:10.1159/000335900

Cited by 13 publications

(7 citation statements)

References 283 publications

(179 reference statements)

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“…The ability of TRPV1 + neurons to both recognize pathogens and trigger type 17 immunity suggests they may be required for initial recognition of extracellular pathogens. The well documented ability of many other skin cell types such as keratinocytes, dendritic cells, and macrophages to recognize extracellular pathogens and the relatively low density of free nerve endings compared with the density of these other cell types in the skin renders a non-redundant role for TRPV1 + neurons in initial pathogen recognition as unlikely (Kashem et al, 2017;de Koning et al, 2012;Naik et al, 2012). In contrast, a unique feature of cutaneous afferents is their ability to transmit signals resulting from pathogen contact or danger over space on a timescale of milliseconds.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous TRPV1+ Neurons Trigger Protective Innate Type 17 Anticipatory Immunity

Cohen

Edwards

Liu

et al. 2019

Cell

261

206

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Section: Discussionmentioning

confidence: 99%

Cutaneous TRPV1+ Neurons Trigger Protective Innate Type 17 Anticipatory Immunity

Cohen

Edwards

Liu

et al. 2019

Cell

261

206

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“…Probably the best explanation is that the relapse is compartmentalized in its early phase, possibly at the level of the skin, which is continuously exposed to pathogen-associated molecular patterns as well as endogenous ligands of pattern recognition receptors (PRRs). Indeed, PRRs were implicated in the pathophysiology of other inflammatory skin diseases, such as AIM2 (absent in melanoma 2) and dectin-1 in psoriasis [ 30 – 32 ]. The IL-1β positive mast cells we recently identified in SchS skin might not only be involved in the chronic urticaria (de Koning et al, submitted), but also in the induction of systemic inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Especially, MRP8/14 and S100A12 are interesting in this regard, as serum levels are associated with disease activity in SchS. Several in vitro studies and mouse models of other inflammatory skin diseases have demonstrated a role for TLR4, e.g., nickel-induced allergic contact dermatitis and graft versus host disease [ 32 ]. Intriguingly, expression of both TLR4 and NLRP3 mRNA is extremely low in healthy epidermis, which one might consider a protective strategy preventing continuous stimulation by constituents of the microbiome, for example [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome

Koning¹,

Schalkwijk²,

Stoffels³

et al. 2015

Arthritis Res Ther

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IntroductionSchnitzler’s syndrome (SchS) is a disabling autoinflammatory disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia, and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers of inflammation and cellular immune responses.MethodsEight patients with SchS received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of inflammation (12 times per patient) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per patient). All data were compared to results of healthy controls.ResultsIL-6 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12 levels correlated with disease activity. In vitro, LPS stimulation resulted in higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients compared to healthy controls, whereas patient cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated patients. Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by IL-1 inhibition. Free light chain levels were elevated in 4 out of 8 patients.ConclusionsIn conclusion, patient PBMCs are hyperresponsive to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is associated with in-vivo and ex-vivo suppression of inflammation. Interestingly, patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our data underscore that IL-1 beta plays a pivotal role in SchS.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0696-0) contains supplementary material, which is available to authorized users.

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“…Last but not least, keratinocytes and sebocytes produce beta-defensins and other antimicrobial peptides [10, 11]. Toll-like receptors are responsible for the recognition of pathogen-associated molecular patterns (PAMPs) and thus form a basis for the differentiation between self- and non-self in innate immunity [4, 12]. …”

Section: Skin As An Immune Organmentioning

confidence: 99%

Steroidogenesis in the skin: Implications for local immune functions

Slominski

Zbytek

Nikolakis

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

329

318

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The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7 -steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases.

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Pattern Recognition Receptors in Immune Disorders Affecting the Skin

Cited by 13 publications

References 283 publications

Cutaneous TRPV1+ Neurons Trigger Protective Innate Type 17 Anticipatory Immunity

Cutaneous TRPV1+ Neurons Trigger Protective Innate Type 17 Anticipatory Immunity

The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome

Steroidogenesis in the skin: Implications for local immune functions

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