Immunolocalization of calcineurin and FKBP12, the FK506-binding protein, in Hassall's corpuscles of human thymus and epidermis

Abstract

Calcineurin, a Ca 2+ /calmodulin-dependent protein phosphatase, plays an important role in various physiological functions including T cell activation. This enzyme is a target molecule for the immunosuppressants, cyclosporin A and FK506. In the present study, we investigated immunohistochemical localization of calcineurin and FKBP12, an FK506-binding protein, in human thymus and epidermis. The catalytic subunit (calcineurin A) of calcineurin was abundantly expressed in Hassall's corpuscles which were localized in the thymic medulla and represented the terminal stages of thymic medullary epithelium. The regulatory subunit (calcineurin B) of calcineurin was also expressed in high amounts in Hassall's corpuscles. In the epidermis, which shows similarities to Hassall's corpuscles, both subunits were also abundantly expressed, and their expression increased with the differentiation of keratinocytes. FKBP12 was observed to be expressed abundantly, both in Hassall's corpuscles and the entire epidermis. These findings suggest that the differentiated forms of the two cell types, which are the thymic medullary epithelial cell and the keratinocyte, are the target for pharmacological actions of FK506.

Effects of drugs and anticytokine antibodies on expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes

“…These proteins are target molecules for ciclosporin A and FK‐506. Their expressions are increased with the differentiation of keratinocytes 29 . On the other hand, ciclosporin A and FK‐506 inhibit keratinocyte proliferation induced by epidemal growth factor, transforming growth factor‐α and IL‐6 30 .…”

The Role of Calcium–Calcineurin–NFAT Signaling Pathway in Health and Autoimmune Diseases

“…Interestingly, the actions of calcineurin inhibitors are not limited to T cells. NFAT1 expression was first described by Northrop et al (120) in mice skin, and then calcineurin expression was subsequently reported in the human epidermis (121). Calcineurin inhibitors reduce antigen presentation by Langerhans' cells and suppress neutrophil chemotaxis through the inhibition of psoriatic monocytes (122).…”

Learning from nudity: lessons from the nude phenotype

“…In thymic epithelial cells that show many intriguing similarities to epidermal keratinocytes (67)(68)(69), overexpression of Wnt 4 or Wnt 5b is associated with an increase in Foxn1 mRNA levels, whereas this is not the case for Wnt 1 (70). This suggests that certain Wnt proteins regulate Foxn1 transcription in thymic epithelial cells and prompts investigations on the regulation of Foxn1 gene transcription in dependence of Wnt signaling in hair follicle keratinocytes where Wnt signaling is crucially implicated in morphogenesis and cycling (71) (Fig.…”