Role of IL-35 in sublingual allergen immunotherapy

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:143

Article

Shamji, Mohamed H.¹  Layhadi, Janice A.¹  Achkova, Daniela¹  Kouser, Lubna¹  Perera-Webb, Alan¹  Couto-Francisco, Natalia C.¹  Parkin, Rebecca V.¹  Matsuoka, Tomokazu¹  Scadding, Guy¹  Ashton-Rickardt, Philip G.²  Durham, Stephen R.¹ 

[1] Imperial Coll London, Natl Heart & Lung Inst, Immunomodulat & Tolerance Grp, Allergy & Clin Immunol,Inflammat Repair & Dev, 1st Floor,Rm 111,Sir Alexander Fleming Bldg, London SW7 2AZ, England

[2] Imperial Coll London, Fac Med, Dept Med, Sect Immunobiol,Div Immunol & Inflammat, London, England

关键词: Seasonal allergic rhinitis;    sublingual immunotherapy;    regulatory T cells;    IL-35;    IL-35-inducible regulatory T cells;   

DOI  :  10.1016/j.jaci.2018.06.041

来源: Elsevier

【 摘 要 】

Background: Grass pollen-specific immunotherapy involves immunomodulation of allergen-specific TH2 responses and induction of IL-10(+) and/ or TGF-beta(+) 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 T(H)2 cells by using flow cytometry and quantitative RT-PCR. Grass pollen-driven T(H)2 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 =5 16), and nonatopic control subjects (NACs; NAC group, n = 16). Results: The SAR group had increased proportions of ILC2s (P = .002) and IL-5 1 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 5.031) and allergen-driven T(H)2 cytokines by effector T cells. IL-35 inhibited CD40 ligand-, IL-4-, and IL-21-mediated IgE production by B cells (P 5.015), allergen-driven T-cell proliferation (P = .001), and T(H)2 cytokine production mediated by primed dendritic cells. iTR35 cells suppressed T(H)2 cell proliferation and cytokine production. In addition, allergen-driven IL-35 levels and iTR35 cell counts were increased in patients receiving SLIT (all, P <.001) and NACs (all, P <.001) compared with patients with SAR. 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.

【 授权许可】

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