Homeostatic Chemokine Research Paper

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Homeostatic chemokines are constitutively expressed and regulate tissue-specific leukocyte migration [117]. The homeostatic chemokine CCL27 also called CTACK (cutaneous T cell-attracting chemokine) is specifically expressed by human epidermal keratinocytes in the skin [118, 119]. CCL27 is expressed in large amounts in basal cells of the epidermis [119]. During the process of epidermal cell differentiation from the basal layer to the skin surface, the expression levels of CCL27 decrease [119]. CCL27 binds to its receptor CCR10 and recruits CLA+ skin-homing memory T cells predominantly to the epidermis [118, 120]. During cutaneous inflammation the proinflammatory cytokines TNF-α and IL-1β can induce an increased expression of CCL27, accompanied …show more content…

In inflammatory skin diseases like psoriasis, allergic-contact dermatitis and atopic dermatitis, the cellular infiltrate is dominated by lymphocytes [119]. Interestingly, these inflammatory skin diseases also show an increased expression of CCL27 and CCR10 [119]. In a lymphocyte-driven in vivo mouse model induced by epicutaneous ovalbumin exposure, mice showed an up-regulation of CCL27 in inflamed skin [119]. When mice were treated with neutralizing antibodies against Ccl27, histological analysis indicated a suppression of inflammation-induced skin thickening, and a substantially decreased leukocyte recruitment into the skin [119]. In previous experiments, my group could show the progressive loss of CCL27 expression during cutaneous carcinogenesis (actinic keratosis, basal cell carcinoma, squamous cell carcinoma) by activation of the EGFR/Ras signaling pathway [69]. EGFR is the activator for Ras signaling, which is activated in a variety of tumors [69, …show more content…

Immunohistochemical analysis of skin tumor samples showed a significantly increased phosphor-Erk1/2 (p-Erk1/2) expression, suggesting a role for MAPK pathway activation in skin tumors [69]. Furthermore, in case of enhanced response rate to epidermal growth factor receptor inhibitor (EGFRI) treatment such as Erlotinib®, tumor patients are observed with inflammatory skin lesions (rash) [69, 92,

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