Role of IL-35 in sublingual allergen immunotherapy
Autor: | Guy W. Scadding, Alan Perera-Webb, Lubna Kouser, Mohamed H. Shamji, Daniela Achkova, Janice A. Layhadi, Natália C. Couto-Francisco, Philip G. Ashton-Rickardt, Stephen R. Durham, Tomokazu Matsuoka, Rebecca Parkin |
---|---|
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Adult Male Thymic stromal lymphopoietin medicine.medical_treatment Immunology Poaceae 03 medical and health sciences Young Adult 0302 clinical medicine medicine Immune Tolerance Immunology and Allergy Humans IL-2 receptor Lymphocytes Antigen-presenting cell Sublingual Immunotherapy CD40 biology Chemistry Interleukins FOXP3 Rhinitis Allergic Seasonal EBI3 Dendritic cell Allergens Middle Aged 030104 developmental biology Cytokine biology.protein Pollen Female 030215 immunology |
Zdroj: | The Journal of allergy and clinical immunology. 143(3) |
ISSN: | 1097-6825 |
Popis: | Background Grass pollen–specific immunotherapy involves immunomodulation of allergen-specific TH2 responses and induction of IL-10+ and/or TGF-β+CD4+CD25+ regulatory T cells (induced Treg cells). IL-35+CD4+CD25+ forkhead box protein 3–negative T (IL-35–inducible regulatory T [iTR35]) cells have been reported as a novel subset of induced Treg cells with modulatory characteristics. Objective We sought to investigate mechanisms underlying the induction and maintenance of immunologic tolerance induced by IL-35 and iTR35 cells. Methods The biological effects of IL-35 were assessed on group 2 innate lymphoid cells (ILC2s); dendritic cells primed with thymic stromal lymphopoietin, IL-25, and IL-33; and B and TH2 cells by using flow cytometry and quantitative RT-PCR. Grass pollen–driven TH2 cell proliferation and cytokine production were measured by using tritiated thymidine and Luminex MagPix, respectively. iTR35 cells were quantified in patients with grass pollen allergy (seasonal allergic rhinitis [SAR] group, n = 16), sublingual immunotherapy (SLIT)–treated patients (SLIT group, n = 16), and nonatopic control subjects (NACs; NAC group, n = 16). Results The SAR group had increased proportions of ILC2s (P = .002) and IL-5+ cells (P = .042), IL-13+ cells (P = .042), and IL-5+IL-13+ ILC2s (P = .003) compared with NACs. 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 effector T cells. IL-35 inhibited CD40 ligand–, IL-4–, and IL-21–mediated IgE production by B cells (P = .015), allergen-driven T-cell proliferation (P = .001), and TH2 cytokine production mediated by primed dendritic cells. iTR35 cells suppressed TH2 cell proliferation and cytokine production. In addition, allergen-driven IL-35 levels and iTR35 cell counts were increased in patients receiving SLIT (all, P Conclusion IL-35 and iTR35 cells are potential novel immune regulators induced by SLIT. The clinical relevance of SLIT can be underscored by restoration of protective iTR35 cells. |
Databáze: | OpenAIRE |
Externí odkaz: |