Zsolt I Komlósi1, Nóra Kovács2, Willem van de Veen3, Anna Isabella Kirsch4, Heinz Benedikt Fahrner5, Marcin Wawrzyniak3, Ana Rebane6, Barbara Stanic7, Oscar Palomares8, Beate Rückert3, Günter Menz4, Mübeccel Akdis3, György Losonczy9, Cezmi A Akdis10. 1. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and CK-CARE: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Department of Pulmonology, Semmelweis University, Budapest, Hungary. Electronic address: drkomlo@yahoo.com. 2. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and CK-CARE: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Lung Health Hospital, Törökbálint, Hungary. 3. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and CK-CARE: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland. 4. Hochgebirgsklinik, Davos-Wolfgang, Switzerland. 5. Department of ENT, Kantonsspital Graubünden, Chur, Switzerland. 6. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and CK-CARE: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia. 7. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and CK-CARE: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; AO Research Institute, Davos, Switzerland. 8. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and CK-CARE: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain. 9. Department of Pulmonology, Semmelweis University, Budapest, Hungary. 10. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and CK-CARE: Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland. Electronic address: akdisac@siaf.uzh.ch.
Abstract
BACKGROUND: Type 3 innate lymphoid cells (ILC3s) are involved in 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. OBJECTIVE: We aimed to investigate the ILC3-B-cell interaction that probably takes place in human tonsils. METHODS: ILC3s were isolated from peripheral blood and palatine tonsils, expanded, and cocultured with naive B cells. Tonsillar ILC3s and regulatory B cells were visualized with immunofluorescence histology. ILC3 frequencies were measured in tonsil tissue of allergic and nonallergic patients and in peripheral blood of allergic asthmatic patients and healthy control subjects. RESULTS: A mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell-activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 ligand (CD40L) expression on circulating and tonsillar ILC3s. IL-15-activated CD40L+ ILC3s helped B-cell survival, proliferation, and differentiation of IL-10-secreting, PD-L1-expressing functional itBreg cells in a CD40L- and B cell-activating factor receptor-dependent manner. ILC3s and regulatory B cells were in close connection with each other in palatine tonsils. ILC3 frequency was reduced in tonsil tissue of allergic patients and in peripheral blood of allergic asthmatic patients. CONCLUSION: Human CD40L+ ILC3s provide innate B-cell help and are involved in an innate immunoregulatory mechanism through induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism, which can contribute to maintenance of immune tolerance, becomes insufficient in allergic diseases.
BACKGROUND: Type 3 innate lymphoid cells (ILC3s) are involved in 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. OBJECTIVE: We aimed to investigate the ILC3-B-cell interaction that probably takes place in human tonsils. METHODS: ILC3s were isolated from peripheral blood and palatine tonsils, expanded, and cocultured with naive B cells. Tonsillar ILC3s and regulatory B cells were visualized with immunofluorescence histology. ILC3 frequencies were measured in tonsil tissue of allergic and nonallergic patients and in peripheral blood of allergic asthmaticpatients and healthy control subjects. RESULTS: A mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell-activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 ligand (CD40L) expression on circulating and tonsillar ILC3s. IL-15-activated CD40L+ ILC3s helped B-cell survival, proliferation, and differentiation of IL-10-secreting, PD-L1-expressing functional itBreg cells in a CD40L- and B cell-activating factor receptor-dependent manner. ILC3s and regulatory B cells were in close connection with each other in palatine tonsils. ILC3 frequency was reduced in tonsil tissue of allergicpatients and in peripheral blood of allergic asthmaticpatients. CONCLUSION:HumanCD40L+ ILC3s provide innate B-cell help and are involved in an innate immunoregulatory mechanism through induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism, which can contribute to maintenance of immune tolerance, becomes insufficient in allergic diseases.
Authors: Sophina H Taitano; Luciën E P M van der Vlugt; Molly M Shea; Jennifer Yang; Nicholas W Lukacs; Steven K Lundy Journal: J Immunol Date: 2018-08-20 Impact factor: 5.422
Authors: Diego Catalán; Miguel Andrés Mansilla; Ashley Ferrier; Lilian Soto; Kristine Oleinika; Juan Carlos Aguillón; Octavio Aravena Journal: Front Immunol Date: 2021-04-29 Impact factor: 7.561
Authors: Márton Szentkereszty; Zsolt István Komlósi; Gergő Szűcs; Gábor Barna; Lilla Tamási; György Losonczy; Gabriella Gálffy Journal: Pathol Oncol Res Date: 2019-05-14 Impact factor: 3.201