1. Dysregulated Responsiveness of Circulating Dendritic Cells to Toll-Like Receptors in ANCA-Associated Vasculitis
- Author
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Régis Josien, Jerome Martin, Karine Amouriaux, Marie Rimbert, Audrey Besançon, Stéphanie Giraudet, Mohamed Hamidou, Marine Aliaga, Caroline Hémont, Cécile Braudeau, Nina Salabert-Le Guen, Caroline Terrien, Antoine Néel, Le Bihan, Sylvie, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d’Immunologie [CHU Nantes] (Centre d’Immunomonitorage Nantes Atlantique - CIMNA), Centre hospitalier universitaire de Nantes (CHU Nantes), Faculté de Médecine - Université de Nantes, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), A grant from the Direction de la Recherche Clinique et de l’Innovation (DRCI), CHU Nantes (#BRD/09/06) to RJ. The CIMNA was supported by the IMBIO-DC program supported by the 'Région des Pays de la Loire'. AN was supported by the Société Nationale Française de Médecine Interne (Bourse Marcel Simon)., ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes], and ANR: ANR11-LABX-0016-01
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dysregulation ,medicine.medical_treatment ,T cell ,anca-associated vasculitis ,Immunology ,Stimulation ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Immunology and Allergy ,dendritic cells ,Original Research ,Whole blood ,030203 arthritis & rheumatology ,Toll-like receptor ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,medicine.disease ,3. Good health ,Cytokine ,medicine.anatomical_structure ,il-12/il-23p40 ,toll-like receptor ,Cytokine secretion ,Granulomatosis with polyangiitis ,Microscopic polyangiitis ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030215 immunology - Abstract
International audience; Objective: Dendritic cells (DCs) are critical effectors of innate and adaptive immunity playing crucial roles in autoimmune responses. We previously showed that blood DC numbers were reduced in autoimmune antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV). Here, we assessed toll-like receptor (TLR) responsiveness of blood DCs from patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).Methods: Blood samples from healthy controls (HCs), GPA, or MPA patients, without treatment, during acute phase (AP) or remission phase (RP) were analyzed. Cytokine production by DCs and T cells was assessed on whole blood by flow cytometry after TLRs or polyclonal stimulation, respectively.Results: We first showed that GPA and MPA are associated with a decreased blood DC number during AP. Conventional DCs (cDCs) from patients with GPA and MPA in AP exhibited a profound decrease of IL-12/IL-23p40 production after TLR3, 4, or 7/8 stimulation compared to patients in remission and HC, with a return to normal values in RP. TNFα secretion was also affected, with a decrease in cDCs from GPA patients in AP after TLR3 stimulation but an increase after TLR7/8 stimulation. By contrast, the responsiveness of plasmacytoid DCs to TLR7 and 9 was only marginally affected. Finally, we observed that IFNγ-producing CD4 + T cell frequency was significantly lower in AP-GPA patients than in HC.Conclusion: We describe, for the first time, a dysregulated response to TLRs of circulating DCs in AAV patients mostly affecting cDCs that exhibit an unexpected reduced inflammatory cytokine secretion possibly contributing to an altered Th cell response.
- Published
- 2017