Th17 and regulatory T cells contribute to the in situ immune response in skin lesions of Jorge Lobo's disease

Med Mycol. 2016 Jan;54(1):23-8. doi: 10.1093/mmy/myv069. Epub 2015 Sep 1.

Abstract

Jorge Lobo's disease (JLD) is a chronic granulomatous mycosis described in various Latin American countries. The main objective of the present study was to investigate the possible role of Th17 and Foxp3+ Treg cells in the pathogenesis of Jorge Lobo's disease. Human skin biopsies were submitted to an immunohistochemistry protocol to detect Foxp3, interleukin (IL)-1beta, CD25, IL-6, IL-17, and IL-23. The epidermis presented acanthosis, hyperkeratosis, and frequent presence of fungi. The dermis presented inflammatory infiltrate comprising macrophages, lymphocytes, epithelioid and multinucleated cells, and an intense number of fungi. Foxp3+ Treg cells and IL-17+ cells were visualized in lymphocytes in the inflammatory infiltrate. IL-1, IL-2R (CD25), IL-6, and IL-23 were visualized in the dermis, intermingled with fungal cells, permeating or participating of the granuloma. Following IL-17, the most prominent cytokine was IL-6. IL-23 and cells expressing CD25 were present in fewer number. The comparative analysis between IL-17 and Foxp3 demonstrated a statistically significant increased number of IL-17+ cells. Th17 cells play a role in the immune response of JLD. IL-1beta and IL-6 added to the previously described increased number of TGF-beta would stimulate such pattern of response. Th17 cells could be present as an effort to modulate the local immune response; however, high levels of a Th17 profile could overcome the role of Treg cells. The unbalance between Treg/Th17 cells seems to corroborate with the less effective immune response against the fungus.

Keywords: Jorge Lobo's Disease; Th17 cells; immune response; regulatory T cells.

MeSH terms

  • Biopsy
  • Female
  • Forkhead Transcription Factors / analysis
  • Humans
  • Immunohistochemistry
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Interleukins / analysis
  • Lobomycosis / pathology*
  • Male
  • Middle Aged
  • Skin / pathology*
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukins