Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:139

Article

Maggi, Laura^1,2  Montaini, Gianni^1,2  Mazzoni, Alessio^1,2  Rossettini, Beatrice^1,2  Capone, Manuela^1,2  Rossi, Maria Caterina^1,2  Santarlasci, Veronica^1,2  Liotta, Francesco^1,2,5,6  Rossi, Oliviero^5,6  Gallo, Oreste⁷  De Palma, Raffaele^3,4  Maggi, Enrico^1,2,5,6  Cosmi, Lorenzo^1,2,5,6  Romagnani, Sergio^1,2  Annunziato, Francesco^1,2,5,6 

[1] Dept Expt & Clin Med, Florence, Italy

[2] DENOTHE Ctr, Florence, Italy

[3] Univ Naples 2, Dept Clin & Expt Med, Naples, Italy

[4] Univ Naples 2, Ctr Biomol Studies Supporting Human Hlth, Naples, Italy

[5] Azienda Osped Careggi, Regenerat Med Unit, Florence, Italy

[6] Azienda Osped Careggi, Immunol & Cellular Therapy Unit, Florence, Italy

[7] Univ Florence, Dept Surg & Translat Med, Florence, Italy

关键词: Group 2 innate lymphoid cell;    TH2;    IL-4;    IL-13;    IL-5;    CD154;    IgE;    Toll-like receptor;   

DOI  :  10.1016/j.jaci.2016.06.032

来源: Elsevier

【 摘 要 】

Background: Protection against helminths consists of adaptive responses by TH2 cells and innate responses by group 2 innate lymphoid cells (ILC2s), with these latter being well characterized in mice but less so in human subjects. Objective: We sought to characterize human circulating ILC2s and compare their functional profile with that of autologous TH2 cells. Methods: Circulating ILC2s and TH2 cells were isolated by means of fluorescence-activated cell sorting and magnetic cell sorting and expanded in vitro. ILC2s were then stimulated with phorbol 12-myristate 13-acetate plus ionomycin, IL-25 plus IL-33 (IL-25/IL-33), or a mixture of Toll-like receptor ligands to evaluate their ability to produce cytokines, express CD154, and induce IgE production by autologous B cells. Cytokines and transcription factor gene methylation were assessed. Results: ILC2s expressed GATA-3, retinoic acid orphan receptor (RORC) 2, and RORa; were able to produce IL-5, IL-13, and IL-4; and, accordingly, were characterized by demethylation of IL4, IL13, IL5, GATA3, and RORC2, whereas the IFNG, IFNG promoter, and TBX21 regions of interest were methylated. ILC2s expressed TLR1, TLR4, and TLR6, and TLR stimulation induced IL-5 and IL-13 production. Moreover, ILC2s expressed CD154 in response to phorbol 12-myristate 13-acetate plus ionomycin, IL-25/ IL-33, or a mixture of TLR ligands. Stimulated ILC2s also induced IgM, IgG, IgA, and IgE production by B cells. Finally, circulating ILC2s from atopic patients were not different in numbers and frequency but expressed higher IL-4 levels than those from nonatopic subjects. Conclusion: This study provides the first evidence that human ILC2s can express CD154 and stimulate the production of IgE by B lymphocytes through IL-25/ IL-33 stimulation or TLR triggering.

【 授权许可】

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