Phenotypic and functional profile of Th17 and Treg cells in allergic fungal sinusitis

作者：Rai Gargi; Das Shukla^*; Ansari Mohammad Ahmad; Singh Praveen Kumar; Gupta Neelima; Sharma Sonal; Akhter Naseem; Ramachandran Vishnampettai G; Haque Shafiul; Dar Sajad Ahmad^*

来源：International Immunopharmacology, 2018, 57: 55-61.

DOI：10.1016/j.intimp.2018.02.009

• Allergic fungal rhinosinusitis
• Aspergillus flavus
• Cytokines
• FoxP3
• RORyt
• T regulatory cells
• Th17 cells

Interleukin-17 producing T helper (Th17) and regulatory T cells (Treg) cells have been identified to play a critical role in atopic inflammation. However, conflicting reports on the role of Th17/Treg cells in allergic fungal rhinosinusitis (AFRS) patients of different ethnicities has mystified its pathogenesis. To better understand the pathophysiological mechanisms involved in AFRS, we conducted a prospective, analytical, case-control study involving 40 confirmed immunocompetent AFRS patients and 20 healthy controls. The distribution of Th17 and Treg cells in PBMC, intracellular mRNA expression of retinoid orphan nuclear receptor (ROR gamma t) in Th17 and forkhead transcription factor (FoxP3) in Treg cells, and serum cytokine levels were investigated. Aspergillus flavus was identified from majority (85%) of patient tissue biopsies. Total serum IgE level along with cytokines IL-17, IL-21, IL-1 beta and TGF-beta were comparatively elevated in AFRS. Nevertheless, IL-2 and IL-10 were reduced. Higher percentages of CD3 (+) CD4 (+) T cells in AFRS with increased expression of CD161 and/or IL-23R markers were observed. Though, lower percentages of CD4 (+) CD25 (+) Treg cells with elevated expression of GITR were patent. Transcription factor ROR gamma t mRNA was upregulated, whereas FoxP3 mRNA was downregulated in AFRS patients. This inclination of Th17/Treg balance towards Th17, and the proposed role of Tregs on Thl and Th2 cells in AFRS, directed us to conclude that Aspergillus infestation may lead to development of atopy and immunological dysbalance inciting a Th17 driven response, thereby, promoting aggravation of nasal polyposis. The observation may provide new insight into the molecular mechanisms leading to revision of the classical paradigm.

• 出版日期2018-4