PMID- 28232832 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 8 DP - 2017 TI - Dysregulated Responsiveness of Circulating Dendritic Cells to Toll-Like Receptors in ANCA-Associated Vasculitis. PG - 102 LID - 10.3389/fimmu.2017.00102 [doi] LID - 102 AB - 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. TNFalpha 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 IFNgamma-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. FAU - Braudeau, Cecile AU - Braudeau C AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France; Institut de Transplantation-Urologie-Nephrologie (ITUN), CHU Nantes, Nantes, France; Centre de Recherche en Transplantation et Immunologie (UMR1064), INSERM, Universite de Nantes, Nantes, France. FAU - Neel, Antoine AU - Neel A AD - Centre de Recherche en Transplantation et Immunologie (UMR1064), INSERM, Universite de Nantes, Nantes, France; Faculte de Medecine, Universite de Nantes, Nantes, France; Service de Medecine Interne, CHU Nantes, Nantes, France. FAU - Amouriaux, Karine AU - Amouriaux K AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, France. FAU - Martin, Jerome C AU - Martin JC AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France; Institut de Transplantation-Urologie-Nephrologie (ITUN), CHU Nantes, Nantes, France; Centre de Recherche en Transplantation et Immunologie (UMR1064), INSERM, Universite de Nantes, Nantes, France; Faculte de Medecine, Universite de Nantes, Nantes, France. FAU - Rimbert, Marie AU - Rimbert M AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France; Institut de Transplantation-Urologie-Nephrologie (ITUN), CHU Nantes, Nantes, France; Centre de Recherche en Transplantation et Immunologie (UMR1064), INSERM, Universite de Nantes, Nantes, France. FAU - Besancon, Audrey AU - Besancon A AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes , Nantes , France. FAU - Giraudet, Stephanie AU - Giraudet S AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes , Nantes , France. FAU - Terrien, Caroline AU - Terrien C AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes , Nantes , France. FAU - Aliaga, Marine AU - Aliaga M AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes , Nantes , France. FAU - Salabert-Le Guen, Nina AU - Salabert-Le Guen N AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France; Centre de Recherche en Transplantation et Immunologie (UMR1064), INSERM, Universite de Nantes, Nantes, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, France. FAU - Hemont, Caroline AU - Hemont C AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France; Institut de Transplantation-Urologie-Nephrologie (ITUN), CHU Nantes, Nantes, France; Centre de Recherche en Transplantation et Immunologie (UMR1064), INSERM, Universite de Nantes, Nantes, France. FAU - Hamidou, Mohamed AU - Hamidou M AD - Centre de Recherche en Transplantation et Immunologie (UMR1064), INSERM, Universite de Nantes, Nantes, France; Faculte de Medecine, Universite de Nantes, Nantes, France; Service de Medecine Interne, CHU Nantes, Nantes, France. FAU - Josien, Regis AU - Josien R AD - CIMNA, Laboratoire d'Immunologie, CHU Nantes, Nantes, France; Institut de Transplantation-Urologie-Nephrologie (ITUN), CHU Nantes, Nantes, France; Centre de Recherche en Transplantation et Immunologie (UMR1064), INSERM, Universite de Nantes, Nantes, France; Faculte de Medecine, Universite de Nantes, Nantes, France; LabEx Immunotherapy Graft Oncology (IGO), Nantes, France. LA - eng PT - Journal Article DEP - 20170209 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC5298972 OTO - NOTNLM OT - ANCA-associated vasculitis OT - IL-12/IL-23p40 OT - dendritic cells OT - dysregulation OT - toll-like receptor EDAT- 2017/02/25 06:00 MHDA- 2017/02/25 06:01 PMCR- 2017/01/01 CRDT- 2017/02/25 06:00 PHST- 2016/11/03 00:00 [received] PHST- 2017/01/20 00:00 [accepted] PHST- 2017/02/25 06:00 [entrez] PHST- 2017/02/25 06:00 [pubmed] PHST- 2017/02/25 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2017.00102 [doi] PST - epublish SO - Front Immunol. 2017 Feb 9;8:102. doi: 10.3389/fimmu.2017.00102. eCollection 2017.