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Contact Hypersensitivity as a Murine Model of Allergic Contact Dermatitis
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CD1d-dependent, iNKT-cell cytotoxicity against keratinocytes in allergic contact dermatitis

Anna Balato1, Yuming Zhao, Erin Harberts

  • 1Department of Dermatology, University of Naples Federico II School of Medicine, Naples, Italy.

Experimental Dermatology
|November 23, 2012
PubMed

Insights

Invariant natural killer T-cells (iNKT-cells) act as effector cells in allergic contact dermatitis (ACD). These cells, found in skin lesions, express cytotoxic molecules, suggesting new therapeutic targets for ACD.

Area of Science:

  • Immunology
  • Dermatology

Background:

  • Allergic contact dermatitis (ACD) traditionally implicates CD8+ T-lymphocytes as primary effector cells.
  • Invariant natural killer T-cells (iNKT-cells) have been observed during the elicitation phase of ACD, suggesting a potential role.

Purpose of the Study:

  • To investigate the capacity of iNKT-cells to function as effector lymphocytes in human ACD.
  • To explore the interactions between iNKT-cells, keratinocytes, and antigen-presenting cells in ACD skin lesions.

Main Methods:

  • In situ staining of skin biopsy specimens from ACD lesions.
  • Analysis of gene expression profiles for cytotoxic effector molecules.
  • Immunostaining to localize cytotoxic granules within iNKT-cells.
  • Studies on antigen presentation by keratinocytes and Langerhans cells to iNKT-cells.

Main Results:

  • Intra-epidermal iNKT-cells were identified in ACD lesions.
  • Significantly elevated expression of perforin and granzymes (A, B, K) was observed in ACD skin compared to normal skin.
  • Cytotoxic granules were localized to iNKT-cells within ACD skin biopsy specimens.
  • Keratinocytes can serve as targets for activated iNKT-cells in a CD1d-dependent manner, but do not activate iNKT-cell cytotoxicity.
  • Mature Langerhans cells did not present glycolipids to iNKT-cells or upregulate CD1d.

Conclusions:

  • iNKT-cells possess the capacity to act as effector cells in human ACD.
  • The findings support the development of inhibitory glycolipids as a therapeutic strategy for ACD.

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