p63 Induces CD4⁺ T-Cell Chemoattractant TARC/CCL17 in Human Epithelial Cells

Abstract

To preserve immunosurveillance, epithelial cells support T-cell trafficking toward inflammatory foci. However, how epithelial cells are enrolled in recruiting T cells has not been fully elucidated. In this study we investigated the function of p63, a p53 family member, in the regulation of the expression of various types of chemokine ligands by focusing on the property of p63 as an epitheliotropic transcription factor. As assessed by experiments using three different human epithelial cell lines with small-interfering RNAs or plasmids of p63, certain CC chemokine ligands were found to be under the control of p63. In these CC chemokine ligands, p63 had the common capacity to upregulate TARC/CCL17 in the different cell lines, whose receptor CCR4 was preferentially presented on CD4(+) T cells such as memory, regulatory, IL-17-producing and type II helper T cells. More interestingly, when cells were stimulated with transforming growth factor-beta (TGF-beta) or epidermal growth factor (EGF) as observed during tissue repair process, the expression of p63 and TARC/CCL17 was concomitantly suppressed. This implies that, in local inflammatory regions with general epithelial tissue remodeling, the p63-TARC/CCL17 axis may participate in the engagement of efficient immune reactions by specified T-cell subsets.

Effect of Narrow-band Ultraviolet B Phototherapy on p63 and MicroRNA (miR-21 and miR-125b) Expression in Psoriatic Epidermis

“…In addition, using a commercially available antibody recognizing all p63 isoforms, we confirmed the similar expression pattern of p63 previously seen in psoriasis and normal epidermis (34). Overall, we found a reverse correlation between miR-21 and TAp63 mRNA levels, which was particularly strong in controls and pre-UV samples.…”

“…p63 is a key molecule for maintenance of epithelial homeostasis and in addition to regulating genes with roles in keratinocyte survival, proliferation, differentiation and adhesion, it controls certain chemokine ligands in human epithelial cells, indicating its role in epithelial immune surveillance (34). responded satisfactorily.…”

CCL17/TARC and CCR4 expression in Merkel cell carcinoma

“…Chemokine (C-C motif) ligand 17/thymus and activation-regulated (CCL17/TARC) is a member of the CC chemokine family, and is highly expressed by thymus and other cells, including keratinocytes, endothelial cells, dendritic cells, bronchial epithelial cells and fibroblasts [ 21 ]. CCL17/TARC acts as a chemoattractant, which primarily aids the recruitment of CD4 + T regulatory cells and Th2, in addition to Th17 cells [ 22 , 23 ]. The effect of CCL17/TARC is mediated by the chemokine receptor CCR4 [ 24 , 25 ].…”

Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation

“…CCL24 chemoattractants secreted from lung epithelial cells or DC’s, direct eosinophils, while CCL17 and CCL22 direct Th2 CD4 + T-cells to the site of inflammation[5, 56–64]. CCL24, CCL17 and CCL22 were increased in OVA immunized mice in comparison to the adjuvant immunized mice as expected in the current model for allergy.…”