Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells

Zsolt I. Komlósi, Nóra Kovács, Willem van de Veen, Anna Isabella Kirsch, Heinz Benedikt Fahrner, Marcin Wawrzyniak, Ana Rebane, Barbara Stanic, Oscar Palomares, Beate Rückert, Günter Menz, Mübeccel Akdis, G. Losonczy, Cezmi A. Akdis

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
DOIs
Publication statusAccepted/In press - Jan 1 2017

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Regulatory B-Lymphocytes
CD40 Ligand
B-Lymphoid Precursor Cells
Palatine Tonsil
Interleukin-10
B-Lymphocytes
Lymphocytes
Interleukin-15
Interleukin-4 Receptors
Cell Differentiation
Maintenance
Immune Tolerance
Immunosuppressive Agents
Cell Communication
Fluorescent Antibody Technique
Cell Survival
Intercellular Signaling Peptides and Proteins
Histology
Healthy Volunteers
Homeostasis

Keywords

  • Allergy
  • Asthma
  • IL-10
  • Immature transitional regulatory B cells
  • Immune tolerance
  • Immunoregulation
  • Regulatory B cells
  • Tonsils
  • Type 3 innate lymphoid cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells. / Komlósi, Zsolt I.; Kovács, Nóra; van de Veen, Willem; Kirsch, Anna Isabella; Fahrner, Heinz Benedikt; Wawrzyniak, Marcin; Rebane, Ana; Stanic, Barbara; Palomares, Oscar; Rückert, Beate; Menz, Günter; Akdis, Mübeccel; Losonczy, G.; Akdis, Cezmi A.

In: Journal of Allergy and Clinical Immunology, 01.01.2017.

Research output: Contribution to journalArticle

Komlósi, ZI, Kovács, N, van de Veen, W, Kirsch, AI, Fahrner, HB, Wawrzyniak, M, Rebane, A, Stanic, B, Palomares, O, Rückert, B, Menz, G, Akdis, M, Losonczy, G & Akdis, CA 2017, 'Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells', Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2017.07.046
Komlósi, Zsolt I. ; Kovács, Nóra ; van de Veen, Willem ; Kirsch, Anna Isabella ; Fahrner, Heinz Benedikt ; Wawrzyniak, Marcin ; Rebane, Ana ; Stanic, Barbara ; Palomares, Oscar ; Rückert, Beate ; Menz, Günter ; Akdis, Mübeccel ; Losonczy, G. ; Akdis, Cezmi A. / Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells. In: Journal of Allergy and Clinical Immunology. 2017.
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T1 - Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells

AU - Komlósi, Zsolt I.

AU - Kovács, Nóra

AU - van de Veen, Willem

AU - Kirsch, Anna Isabella

AU - Fahrner, Heinz Benedikt

AU - Wawrzyniak, Marcin

AU - Rebane, Ana

AU - Stanic, Barbara

AU - Palomares, Oscar

AU - Rückert, Beate

AU - Menz, Günter

AU - Akdis, Mübeccel

AU - Losonczy, G.

AU - Akdis, Cezmi A.

PY - 2017/1/1

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N2 - 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.

AB - 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.

KW - Allergy

KW - Asthma

KW - IL-10

KW - Immature transitional regulatory B cells

KW - Immune tolerance

KW - Immunoregulation

KW - Regulatory B cells

KW - Tonsils

KW - Type 3 innate lymphoid cells

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