Cécile Braudeau1, Karine Amouriaux2, Antoine Néel3, Guillaume Herbreteau4, Nina Salabert5, Marie Rimbert1, Jérôme C Martin6, Caroline Hémont1, Mohamed Hamidou7, Régis Josien8. 1. CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France. 2. CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, F-44000, France. 3. INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; CHU Nantes, Service de Médecine Interne, Nantes, F-44000, France. 4. CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France. 5. CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, F-44000, France. 6. CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; Université de Nantes, Faculté de Médecine, Nantes, F-44000, France. 7. INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, Faculté de Médecine, Nantes, F-44000, France; CHU Nantes, Service de Médecine Interne, Nantes, F-44000, France. 8. CHU Nantes, Laboratoire d'Immunologie, Center for Immunomonitoring Nantes Atlantic (CIMNA), Nantes, F-44000, France; INSERM, U1064, Center for Research in Transplantation and Immunology, ITUN, Nantes, F-44000, France; Université de Nantes, UMR_S 1064, Nantes, F-44000, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, F-44000, France; Université de Nantes, Faculté de Médecine, Nantes, F-44000, France. Electronic address: Regis.josien@univ-nantes.fr.
Abstract
OBJECTIVE: Mucosal associated invariant T cells (MAIT) and innate lymphoid cells (ILCs) have immunoregulatory functions at mucosal sites and have been involved in various inflammatory and autoimmune diseases. The aim of this study was to assess their frequencies in blood in ANCA-associated vasculitis (AAV). METHODS: The frequencies and function of MAIT cells, ILCs, γδT, iNKT, NK cells were analyzed by flow cytometry on PBMC of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) without any treatment, in acute (AP) and remission phase (RP) and compared with healthy controls (HC). RESULTS: The frequencies of MAIT cells were strongly decreased in GPA and MPA in AP compared to HC, both in never treated and in relapsing patients and independently of patient age. This was associated with an activated phenotype of patient MAIT cells, as shown by increased expression of CD69 and IFNγ. MAIT cells remained decreased during RP in AAV patients. The frequencies of iNKT and γδT cells were unaffected compared to HC, whereas those of NK cells were slightly reduced during AP in MPA. We also observed a significant decrease in frequencies of total ILCs with decreased ILC2 and ILC3 and increased ILC1 during AP in both GPA and MPA compared to HC. These frequencies normalized during RP. Interestingly, we observed a significant correlation between the frequency of total ILCs and BVAS. CONCLUSION: We show for the first time that AAV are associated with a major decrease and an activated phenotype of blood MAIT cell. These features persisted during remission suggesting a role for MAIT cells in the pathogenesis of AAV.
OBJECTIVE: Mucosal associated invariant T cells (MAIT) and innate lymphoid cells (ILCs) have immunoregulatory functions at mucosal sites and have been involved in various inflammatory and autoimmune diseases. The aim of this study was to assess their frequencies in blood in ANCA-associated vasculitis (AAV). METHODS: The frequencies and function of MAIT cells, ILCs, γδT, iNKT, NK cells were analyzed by flow cytometry on PBMC of patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) without any treatment, in acute (AP) and remission phase (RP) and compared with healthy controls (HC). RESULTS: The frequencies of MAIT cells were strongly decreased in GPA and MPA in AP compared to HC, both in never treated and in relapsing patients and independently of patient age. This was associated with an activated phenotype of patient MAIT cells, as shown by increased expression of CD69 and IFNγ. MAIT cells remained decreased during RP in AAV patients. The frequencies of iNKT and γδT cells were unaffected compared to HC, whereas those of NK cells were slightly reduced during AP in MPA. We also observed a significant decrease in frequencies of total ILCs with decreased ILC2 and ILC3 and increased ILC1 during AP in both GPA and MPA compared to HC. These frequencies normalized during RP. Interestingly, we observed a significant correlation between the frequency of total ILCs and BVAS. CONCLUSION: We show for the first time that AAV are associated with a major decrease and an activated phenotype of blood MAIT cell. These features persisted during remission suggesting a role for MAIT cells in the pathogenesis of AAV.
Authors: Guillermo Carvajal Alegria; Pierre Gazeau; Sophie Hillion; Claire I Daïen; Divi Y K Cornec Journal: Clin Rev Allergy Immunol Date: 2017-10 Impact factor: 8.667
Authors: B Fazekas; A Moreno-Olivera; Y Kelly; P O'Hara; S Murray; A Kennedy; N Conlon; J Scott; A M Melo; F B Hickey; D Dooley; E C O'Brien; S Moran; D G Doherty; M A Little Journal: Clin Exp Immunol Date: 2017-10-20 Impact factor: 4.330
Authors: Peter Lamprecht; Anja Kerstein; Sebastian Klapa; Susanne Schinke; Christian M Karsten; Xinhua Yu; Marc Ehlers; Jörg T Epplen; Konstanze Holl-Ulrich; Thorsten Wiech; Kathrin Kalies; Tanja Lange; Martin Laudien; Tamas Laskay; Timo Gemoll; Udo Schumacher; Sebastian Ullrich; Hauke Busch; Saleh Ibrahim; Nicole Fischer; Katrin Hasselbacher; Ralph Pries; Frank Petersen; Gesche Weppner; Rudolf Manz; Jens Y Humrich; Relana Nieberding; Gabriela Riemekasten; Antje Müller Journal: Front Immunol Date: 2018-04-09 Impact factor: 7.561