Human CD40L-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells

Publication date: Available online 20 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Zsolt István Komlósi, Nóra Kovács, Willem van de Veen, Anna Kirsch, Heinz Benedikt Fahrner, Marcin Wawrzyniak, Ana Rebane, Barbara Stanic, Oscar Palomares, Beate Rückert, Günter Menz, Mübeccel Akdis, György Losonczy, Cezmi A. Akdis
BackgroundType 3 innate lymphoid cells (ILC3s) are involved in the maintenance of mucosal homeostasis; however, their role in immunoregulation has been unknown. Immature transitional regulatory B (itBreg) cells are innate-like B cells with immunosuppressive properties, and the in vivo mechanisms by which they are induced have not been fully clarified.ObjectiveWe aimed to investigate the ILC3-B cell interaction that probably takes place in human tonsils.MethodsILC3s were isolated from peripheral blood and palatine tonsils, expanded and cocultured with naïve B cells. Tonsillar ILC3s and Breg cells were visualized with immunofluorescence histology. The frequencies of ILC3s were measured in tonsil tissue of allergic and non-allergic patients; and in peripheral blood of allergic asthmatics and healthy controls.ResultsA mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells via BAFF-receptor, while IL-15, a potent growth factor for ILC3s, induced the expression of CD40L on circulating and tonsillar ILC3s. IL-15-activated CD40L⁺ILC3s helped B cell survival, proliferation and the differentiation of IL-10-secreting, functional itBreg cells in a CD40L- and BAFF-receptor-dependent manner. ILC3s and Breg cells were in close connection with each other in palatine tonsils. The frequency of ILC3s was reduced in tonsil tissue of allergic patients and in peripheral blood of allergic asthmatics.ConclusionHuman CD40L⁺ILC3s provide innate B cell help, and are involved in an innate immunoregulatory mechanism by the induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism may contribute to the maintenance of the immune tolerance and become insufficient in allergic diseases.

Graphical abstract

Teaser

ILC3-mediated induction of Breg cells is a novel, innate immunoregulatory mechanism that may contribute to the maintenance of immune tolerance and become insufficient in allergy, as the frequency of ILC3s is reduced in allergic diseases.


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