Deficient cutaneous antibacterial competence in cutaneous T-cell lymphomas: role of Th2-mediated biased Th17 function.

Abstract

PURPOSE:

Primary cutaneous T-cell lymphomas (CTCL) are neoplastic disorders of skin-homing T cells. Affected skin areas show morphologic similarities with alterations in other T-cell-mediated dermatoses. Furthermore, as in atopic dermatitis but in contrast with psoriasis, patients with CTCL are frequently afflicted by cutaneous bacterial infections that support the survival of lymphoma cells. Our aim was to investigate the mechanisms of elevated susceptibility to cutaneous infections in patients with CTCL.

EXPERIMENTAL DESIGN:

Skin samples from CTCL, psoriasis, and atopic dermatitis patients were used to illuminate the antibacterial competence status and the presence of its modulating cytokines. For substantiation of findings, 3-dimensional epidermis models, isolated and in vitro generated Th-subpopulations, were applied. Parameters were analyzed via qPCR and IHC.

RESULTS:

CTCL lesions compared with psoriatic lesions presented an impaired upregulation of antibacterial proteins (ABPs), with levels even below those in atopic dermatitis. This was associated with a relative deficiency of the ABP-inducing cytokine IL-17 and a strong presence of the ABP-downregulating cytokine IL-13. The simultaneous presence of the Th17-cell cytokine IL-26 indicated that IL-17 deficiency in CTCL lesions results from functional deviation of Th17 cells. Accordingly, IL-17 but not IL-26 production by Th17 cells in vitro was inhibited by IL-4Rα ligand. Levels of other ABP inducers were comparable between CTCL and psoriasis lesions. The same was true about IL-22/TNF-α targets, including the keratinocyte hyper-regeneration marker K16 and the matrix-degrading enzyme MMP1.

CONCLUSION:

Our results suggest that the cutaneous bacterial infections in CTCL are caused by impaired ABP induction as consequence of Th2-mediated biased Th17-cell function.

• Authors: Kerstin Wolk, Hiroshi Mitsui, Katrin Witte, Sylke Gellrich, Nicholas Gulati, Daniel Humme, Ellen Witte, Melanie Gonsior, Marc Beyer, Marshall E Kadin, Hans-Dieter Volk, James G Krueger, Wolfram Sterry, Robert Sabat
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 21 Pg. 5507-16 (Nov 01 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 25212608 (Publication Type: Journal Article)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Anti-Bacterial Agents
• Interleukins
• Tumor Necrosis Factor-alpha
• MMP1 protein, human
• Matrix Metalloproteinase 1

Topics

• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (immunology)
• Cells, Cultured
• Dermatitis, Atopic (immunology)
• Epidermis (immunology)
• Female
• Humans
• Interleukins (immunology)
• Keratinocytes (immunology)
• Lymphoma, T-Cell, Cutaneous (immunology)
• Male
• Matrix Metalloproteinase 1 (immunology)
• Middle Aged
• Psoriasis (immunology)
• Skin Neoplasms (immunology)
• Th17 Cells (immunology)
• Th2 Cells (immunology)
• Tumor Necrosis Factor-alpha (immunology)