Lesional psoriatic T cells contain the capacity to induce a T cell activation molecule CDw60 on normal keratinocytes

L Skov1, L S Chan, D A Fox

  • 1Department of Dermatology, Gentofie Hospital, University of Copenhagen, Denmark.

Insights

In psoriatic skin, T cells upregulate CDw60 on keratinocytes, partly via IL-13. This suggests a new mechanism for T cell involvement in psoriasis pathogenesis.

Area of Science:

  • Dermatology
  • Immunology
  • Cell Biology

Background:

  • Psoriatic skin exhibits altered keratinocyte characteristics.
  • CDw60, a ganglioside antigen, is expressed on keratinocytes.
  • The role of T cells in modulating CDw60 expression in psoriasis is unclear.

Purpose of the Study:

  • To investigate CDw60 expression in psoriatic skin keratinocytes.
  • To determine if T cell factors induce CDw60 overexpression on keratinocytes.
  • To identify specific T cell cytokines involved in CDw60 modulation.

Main Methods:

  • Analysis of CDw60 expression on basal and suprabasal keratinocytes in psoriatic skin.
  • Characterization of CDw60 antigen using monoclonal antibody UM4D4 and neuraminidase treatment.
  • Cloning of T cell lines from psoriatic lesions.
  • Incubation of normal keratinocytes with T cell clones and specific cytokines (IL-2, IL-3, IL-4, IL-6, IL-13, TGF-β, GM-CSF, IFN-γ).
  • Assessment of CDw60 expression modulation by T cell factors and cytokines.

Main Results:

  • CDw60 is expressed on basal and suprabasal keratinocytes in psoriatic skin.
  • CDw60 antigen is identified as the 9-O-acetylated disialosyl group on ganglioside GD3.
  • Activated T cell clones from psoriatic lesions up-regulated CDw60 expression on normal keratinocytes.
  • Interleukin-4 (IL-4) and Interleukin-13 (IL-13) strongly upregulated keratinocyte CDw60 expression.
  • Interferon-gamma (IFN-γ) downregulated keratinocyte CDw60 expression.
  • Anti-IL-13 partially neutralized the T cell supernatant-induced CDw60 upregulation.

Conclusions:

  • CDw60 expression on psoriatic epidermal keratinocytes is likely induced by intralesionally activated T cells.
  • IL-13 plays a significant role in the T-cell-mediated upregulation of CDw60.
  • This represents a novel mechanism of T cell participation in psoriasis pathogenesis.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Renewal of Skin Epidermal Stem Cells01:12

Renewal of Skin Epidermal Stem Cells

The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular cells,...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...