A Comprehensive Analysis of Pattern Recognition Receptors in Normal and Inflamed Human Epidermis: Upregulation of Dectin-1 in Psoriasis

Abstract

Human epidermis plays an important role in host defense by acting as a physical barrier and signaling interface between the environment and the immune system. Pattern recognition receptors (PRRs) are crucial to maintain homeostasis and provide protection during infection, but are also causally involved in monogenic auto-inflammatory diseases. This study aimed to investigate the epidermal expression of PRRs and several associated host defense molecules in healthy human skin, psoriasis, and atopic dermatitis (AD). Using microarray analysis and real-time quantitative PCR, we found that many of these genes are transcribed in normal human epidermis. Only a few genes were differentially induced in psoriasis (CLEC7A (dectin-1), Toll-like receptor (TLR) 4, and mannose receptor C type 1 (MRC1)) or AD (MRC1, IL1RN, and IL1β) compared with normal epidermis. A remarkably high expression of dectin-1 mRNA was observed in psoriatic epidermis and this was corroborated by immunohistochemistry. In cultured primary human keratinocytes, dectin-1 expression was induced by IFN-γ, IFN-α, and Th17 cytokines. Keratinocytes were unresponsive, however, to dectin-1 ligands such as β-glucan or heat-killed Candida albicans, nor did we observe synergy with TLR2/TLR5 ligands. In conclusion, upregulation of dectin-1 in psoriatic lesions seems to be under control of psoriasis-associated cytokines. Its role in the biology of skin inflammation and infection remains to be explored.

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

“…In contrast, gal-8 and gal-9 expression was similar in all three types of sample ( Fig 1A). Dectin-1 was detected at high level in lesional skin, in agreement with a recent report [17].…”

Pattern Recognition Receptors in Immune Disorders Affecting the Skin

“…Several groups investigated PRR expression in psoriatic lesions. Lesional TLR2 mRNA and protein expression levels are similar to those in normal skin [15,16], although two older studies suggested differently [17,18]. Transforming growth factor alpha, which is induced in psoriasis, was shown to increase TLR5 and TLR9 expression and function in keratinocytes.…”

“…Also, TLR2, TLR3 and TLR4 ligands were shown to induce the psoriasis-associated cytokine TNF-α in human keratinocytes [18]. It is, however, controversial whether TLR4 is expressed in primary human keratinocytes, because several authors did not find TLR4 expression or effects of lipopolysaccharide (LPS) stimulation in these cells [15,20]. …”

“…Transforming growth factor alpha, which is induced in psoriasis, was shown to increase TLR5 and TLR9 expression and function in keratinocytes. TLR2, TLR5 and TLR9 ligands induce the expression of human β-defensins in primary keratinocytes [15,19]. Also, TLR2, TLR3 and TLR4 ligands were shown to induce the psoriasis-associated cytokine TNF-α in human keratinocytes [18].…”

The mycobiome of the human urinary tract: potential roles for fungi in urology

“…Alterations in the mycobiome occurring in the absence of classical infections have been implicated in a wide range of diseases, such as chronic hepatitis B virus (HBV) hepatitis (25), atopic dermatitis (71), dandruff (72), IBD (73)(74)(75), cystic fibrosis (24), allergy/atopy (64), asthma (76), and psoriasis (77,78). There is no obvious pattern of fungal alterations in these diseases; pathology can be associated with either a decreased or increased diversity from that seen in the healthy state.…”