Speculations on the Immunopathogenesis of Psoriasis: T-Cell Violation of a Keratinocyte Sphere of Influence

Abstract

The thesis is advanced that the differences in antigen processing and presentation described for "fresh" and "cultured" Langerhans cells in vitro reflect similar differences between intraepidermal and intranodal Langerhans cells in vivo. The functional properties of Langerhans cells are dependent upon the microenvironment in which they reside; thus, intraepidermal Langerhans cells are under the influence of cytokines secreted by keratinocytes, whereas intranodal Langerhans cells come under the influence of lymphokines from T lymphocytes. It is speculated that a genetic lesion in psoriasis robs keratinocytes of their capacity to create an "appropriate" epidermal microenvironment. As a consequence, intraepidermal Langerhans cells adopt the functional program of intranodal cells. When "uninvolved" psoriatic skin receives a cutaneous challenge with antigen, Langerhans cells, by activating naive T cells in situ, unwittingly engender a microenvironment that is more appropriate to a lymph node. This skin becomes "involved" as it gradually acquires features associated with lymph nodes (such as high endothelial venules). And the derangement is further complicated by abnormalities of proliferation and differentiation among keratinocytes and dermal fibroblasts as they respond to the inappropriate T-cell-derived lymphokines, giving rising to the typical, active psoriatic lesion.