Innate immune modulation of keratinocytes by antikeratin 16 antibodies

Wu, Chuanbin; Li, Chang-Jiu; Wei, Liming; Zhang, Zheng

doi:10.1111/j.1600-0625.2007.00682.x

Cited by 18 publications

(9 citation statements)

References 45 publications

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“…Autoantibodies to KRT16 have been tied to an exaggerated activation of innate immunity signaling pathways in psoriatic lesions (57,58). Furthermore, IL-1a treatment of human primary keratinocytes elicits a transcriptional profile enriched in antimicrobial peptides and genes from the epidermal differentiation complex (59) that is strikingly similar to challenged Krt16 −/− skin and to Krt16's association with skin barrier-related factors as revealed by computational analysis.…”

Section: Krt16 -/-Control Krt16mentioning

confidence: 99%

Keratin 16 regulates innate immunity in response to epidermal barrier breach

Lessard

Piña-Paz

Rotty

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

167

179

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Mutations in the type I keratin 16 (Krt16) and its partner type II keratin 6 (Krt6a, Krt6b) cause pachyonychia congenita (PC), a disorder typified by dystrophic nails, painful hyperkeratotic calluses in glabrous skin, and lesions involving other epithelial appendages. The pathophysiology of these symptoms and its relationship to settings in which Krt16 and Krt6 are induced in response to epidermal barrier stress are poorly understood. We report that hyperkeratotic calluses arising in the glabrous skin of individuals with PC and Krt16 null mice share a gene expression signature enriched in genes involved in inflammation and innate immunity, in particular damage-associated molecular patterns. Transcriptional hyper-activation of damage-associated molecular pattern genes occurs following de novo chemical or mechanical irritation to ear skin and in spontaneously arising skin lesions in Krt16 null mice. Genome-wide expression analysis of normal mouse tail skin and benign proliferative lesions reveals a tight, context-dependent coregulation of Krt16 and Krt6 with genes involved in skin barrier maintenance and innate immunity. Our results uncover a role for Krt16 in regulating epithelial inflammation that is relevant to genodermatoses, psoriasis, and cancer and suggest a avenue for the therapeutic management of PC and related disorders.

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Section: Krt16 -/-Control Krt16mentioning

confidence: 99%

Keratin 16 regulates innate immunity in response to epidermal barrier breach

Lessard

Piña-Paz

Rotty

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

167

179

View full text Add to dashboard Cite

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“…Interestingly, anti-keratin 16 antibodies are highly concentrated in the serum of psoriasis patients and may be involved in chronic inflammation. Keratinocytes incubated with mouse antikeratin 16 monoclonal, antibodies have increased levels of TLR 2, TLR 4, involucrin, and NF- κ B nascent polypeptide-associated complex mRNA [113]. As implied earlier, psoriasis is a T cell-mediated disease caused in part by activated T cells interacting with antigen-presenting cells (APCs) in addition to IFN- γ , IL-1, and TNF- α effects [114, 115].…”

Section: Tlrs In Dermatologic Diseasementioning

confidence: 99%

Toll-Like Receptors: Role in Dermatological Disease

Hari

Flach

Shi

et al. 2010

Mediators of Inflammation

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Toll-like receptors (TLRs) are a class of conserved receptors that recognize pathogen-associated molecular patterns (PAMPs) present in microbes. In humans, at least ten TLRs have been identified, and their recognition targets range from bacterial endotoxins to lipopeptides, DNA, dsRNA, ssRNA, fungal products, and several host factors. Of dermatological interest, these receptors are expressed on several skin cells including keratinocytes, melanocytes, and Langerhans cells. TLRs are essential in identifying microbial products and are known to link the innate and adaptive immune systems. Over the years, there have been significant advances in our understanding of TLRs in skin inflammation, cutaneous malignancies, and defence mechanisms. In this paper, we will describe the association between TLRs and various skin pathologies and discuss proposed TLR therapeutics.

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“…Keratinocytes express various types of receptors to sense invading pathogens, which include Toll-like receptors (TLRs) and protease-activated receptors (PARs). Human keratinocytes express all TLRs except for TLR-7 and -8, [30][31][32][33][34] indicating an ability to recognize constituents of microorganisms, such as bacterial lipopeptides, peptidoglycan and flagellin, lipopolysaccharides (LPS), single-and double-stranded RNA and unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides of bacterial DNA. In dogs, canine keratinocyte progenitor cell line (CPEK) was shown to induce transcription of tlr-1, tlr-2, tlr-4 and tlr-6.…”

Section: Cutaneous Immune Reactionsmentioning

confidence: 99%