Role of interleukin-35 in sublingual allergy immunotherapy
| Autor: | Shamji, MH, Layhadi, JA, Achkova, D, Kouser, L, Perera-Webb, A, Couto-Francisco, NC, Parkin, R, Matsuoka, T, Scadding, G, Ashton-Rickardt, PG, Durham, SR |
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| Přispěvatelé: | Medical Research Council (MRC) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Allergy MONOCLONAL-ANTIBODY Immunology Seasonal allergic rhinitis INNATE LYMPHOID-CELLS Poaceae sublingual immunotherapy regulatory T cells TYPE-2 Young Adult HUMAN B-CELLS INFLAMMATION IL-35-inducible regulatory T cells WORLD Immune Tolerance Humans REGULATORY T-CELLS Lymphocytes IL-35–inducible regulatory T cells Science & Technology Interleukins RHINITIS Rhinitis Allergic Seasonal Allergens Middle Aged 1107 Immunology IL-35 ASTHMA Pollen Female iT(R)35 cells Life Sciences & Biomedicine RESPONSES |
| Zdroj: | 1142.e4 |
| Popis: | BACKGROUND: Grass pollen-specific immunotherapy involves immunomodulation of allergen-specific T helper 2 cell (Th2) responses and induction of IL-10+ and/or TGF-β+CD4+CD25+ regulatory T cells (iTregs). IL-35+CD4+CD25+Foxp3- T (iTR35) cells have been reported as a novel subset of iTregs with modulatory characteristics. OBJECTIVE: To investigate the mechanisms underlying the induction and maintenance of immunological tolerance induced by IL-35 and iTR35 cells. METHODS: The biological effects of IL-35 was assessed on Group II innate lymphoid cells (ILC2s), dendritic cells (DCs) primed with TSLP, IL-25 and IL-33, B and Th2 cells by flow cytometry and qRT-PCR. Grass pollen-driven Th2 cell proliferation and cytokine production was measured by [3H]-thymidine and Luminex MagPix, respectively. iTr35 cells were quantified in grass pollen allergics (SAR, n=16), sublingual immunotherapy-treated patients (SLIT, n=16) and non-atopic controls (NAC, n=16). RESULTS: SAR had elevated proportions of ILC2s (P=.002), IL5+ (P=.042), IL13+ (P=.042) and IL5+IL13+ILC2s (P=.003) compared to NAC. IL-35 inhibited IL-5 and IL-13 production by ILC2s in the presence of IL-25 or IL-33 (P=.031) and allergen-driven Th2 cytokines by Teff cells. IL-35 inhibited CD40L, IL-4 and IL-21-mediated IgE production by B cells (P=.015), allergen-driven T cell proliferation (P=.001) and Th2 cytokine production by primed DCs. iTR35 cells suppressed Th2 cell proliferation and cytokine production. In addition, allergen-driven IL-35 levels and iTR35 cells were elevated in SLIT (all, P |
| Databáze: | OpenAIRE |
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