الفهرس 
PsoriasisOnly 14 pages are availabe for public view
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Abstract
Psoriasis is a common, chronic, inflammatory skin disorder affecting 1-3% of the world population. It is considered a genetically determined disorder that can be triggered by various environmental stimuli. The exact pathophysiology of psoriasis is not fully understood, yet it is now a fact that both innate and adaptive immunity play an important role in its pathogenesis.
TLRs are a major class of PRRs that are involved in detecting invading pathogens in the skin and initiating cutaneous immune response. Ten TLRs are identified in humans, all of which share similarities in their structure and function, but respond to different microbial components or endogenous ligands. There are differences among the TLR signaling pathways which leads to the different immune responses against given stimuli.
Different TLRs are present on a large number of immune cells and epithelial cells all over the body. In the skin, many types of cells express TLRs as KCs and LCs in the epidermis. TLRs participate in cutaneous host defense mechanisms against various skin infections caused by common bacterial, fungal, and viral pathogens including S aureus, C albicans and HSV. In addition, certain TLRs have been implicated in the pathogenesis of some skin diseases such as acne vulgaris and atopic dermatitis. As for psoriasis, few authors have conceived that TLRs may have a role in its pathogenesis.
This study included 20 patients with chronic plaque psoriasis with their ages ranging from 10-65 years, and 10 healthy controls with an age range from 12-60 years. Patients were classified according to the clinical severity of psoriasis by PASI score into 3 groups: mild, moderate and severe. Punch biopsies were taken from the non-lesional and lesional skin of patients and from controls, stained and examined under light microscope. The immunoreactivity of TLR1 and TLR2 in the different epidermal layers was studied using IRIDI score. Their expression in the dermis was also evaluated. The relation between the intensity of TLR1 and TLR2 expression and the severity of psoriasis on one hand, and the duration of illness on the other hand were studied.
It was found that normal human skin expressed both TLR1 and TLR2, where cytoplasmic TLR1 expression was detected only in the KCs of the basal and the suprabasal layers of all control samples. Normal skin showed cytoplasmic TLR2 immunoreactivity of the basal KCs in all specimens, with variable intensities of staining in suprabasal and upper epidermal layers. In contrast to normal skin, the expression of TLR1 and TLR2 was present predominating in the upper epidermal KCs of lesional psoriatic skin with different grades of staining of the rest of the epidermis. The staining pattern was cytoplasmic, nuclear or both. Positive staining of the dermal inflammatory infiltrate for TLR1 and TLR2 was seen in most of the samples.
The differential IRIDI scores of TLR1 and TLR2 in the basal and the suprabasal layers, as well as the total IRIDI were higher in normal compared with lesional psoriatic skin. On the contrary, the superficial cell layer showed higher IRIDI in lesional psoriatic than normal skin.These results support the variability of TLR expression between normal and psoriatic skin.
Comparing IRIDI scores of TLR1 and TLR2 expression in the different groups of patients revealed no significant differences between any of the groups in either the total or the differential IRIDI scores. In addition, no significant correlations were found between any of IRIDI scores (total and differential) for TLR1 or TLR2 expression and PASI score of the patients.
In conclusion, the present study has shown that TLR1 and TLR2 are expressed in the epidermis of the normal skin where they probably play a protective role against infections by various microbial agents. Moreover, modulation of TLR expression has been demonstrated in skin lesions of psoriasis where both TLR1 and TLR2 are more highly expressed on KCs of the upper epidermis than the basal layer with decrease in the total amount of TLR1 and TLR2 in psoriatic compared with normal skin. Accordingly, TLR1 and TLR2 may play an essential role in the pathogenesis of psoriasis. In addition, there is no significant correlation between TLR1 or TLR2 expression and either the age, sex of the patients or the severity and the duration of psoriasis.
Finally, further research on a larger scale of patients studying the role of the different TLRs (TLR1-TLR10) in normal skin as well as in the clinical variants of psoriasis is recommended. This will help in better understanding the pathogenesis of psoriasis, and thus open the way for the design of new and efficient drugs to treat this puzzling disease.