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Clinical outcome and IL‐17, IL‐23, IL‐27 and FOXP3 expression in peripheral blood mononuclear cells of pollen‐allergic children during sublingual immunotherapy
Author(s) -
Nieminen Kaisa,
Valovirta Erkka,
Savolainen Johannes
Publication year - 2010
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/j.1399-3038.2009.00920.x
Subject(s) - medicine , foxp3 , peripheral blood mononuclear cell , immunology , allergy , slit , immunotherapy , interleukin 4 , cytokine , immune system , biology , biochemistry , genetics , in vitro
Nieminen K, Valovirta E, Savolainen J. Clinical outcome and IL‐17, IL‐23, IL‐27 and FOXP3 expression in peripheral blood mononuclear cells of pollen‐allergic children during sublingual immunotherapy.
Pediatr Allergy Immunol 2010: 21: e174–e184.
© 2009 John Wiley & Sons A/S Induction of allergen‐specific, tolerogenic, IL‐10 and/or TGF‐β‐producing T‐regulatory (Treg) cells that express transcription factor FOXP3 is considered as one of the key mechanisms of allergen‐specific immunotherapy. However, little is known of the induction of FOXP3 expression in children during sublingual immunotherapy (SLIT). Recently, also, a novel subgroup of T‐helper (Th) cells, the Th17 cells, secreting predominantly IL‐17 (IL‐17A), was identified. The expressions of IL‐17 or the Th17‐regulating cytokines IL‐23 and IL‐27 during SLIT are currently completely unexplored. This randomized, placebo‐controlled dose‐response study was performed to analyze the effects of SLIT on FOXP3, IL‐17, IL‐23, and IL‐27 expressions in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis and their associations with clinical outcome. Thirty children were included: ten received SLIT with a glycerinated mixture of birch, hazel and alder with a cumulative weekly dose of 24,000 SQ‐U, 10 with dose 200,000 SQ‐U/wk, and ten received placebo. Cytokine and FOXP3 mRNA expressions in allergen‐, purified protein derivative‐stimulated and non‐stimulated PBMC were determined at 0, 1 and 2 yr of SLIT by real‐time RT‐PCR (TaqMan®). Symptoms and medications were recorded using diary cards. Allergen‐induced IL‐17 mRNA expression was significantly increased in the study subjects with elevated combined Symptom Medication Score (SMS) after 2 yr. There was also a significant positive correlation between the allergen‐induced IL‐17 and SMS in whole study group ( r = 0.38, p = 0.039) and especially the 200,000 SQ‐U dose‐treated group ( r = 0.74, p = 0.027) at 2 yr. Allergen‐induced FOXP3 mRNA expression was significantly increased in the 200,000 SQ‐U dose‐treated children after two study years as compared with baseline (p = 0.016) and placebo‐treated children (p = 0.028). The changes in FOXP3 mRNA expression positively correlated with IL‐10 and TGF‐β mRNAs during SLIT in whole study population. Increased allergen‐induced IL‐17 responses during SLIT are associated with elevated SMS. Increased tolerogenic, allergen‐specific Treg responses are also observed in children during SLIT.