pDC therapy induces recovery from EAE by recruiting endogenous pDC to sites of CNS inflammation.
Plasmacytoid dendritic cells (pDCs) exhibit both innate and adaptive functions. In particular they are the main source of type I IFNs and directly impact T cell responses through antigen presentation. We have previously demonstrated that during experimental autoimmune encephalomyelitis (EAE) initiation, myelin-antigen presentation by pDCs is associated with suppressive Treg development and results in attenuated EAE. Here, we show that pDCs transferred during acute disease phase confer recovery from EAE. Clinical improvement is associated with migration of injected pDCs into inflamed CNS and is dependent on the subsequent and selective chemerin-mediated recruitment of endogenous pDCs to the CNS. The protective effect requires pDC pre-loading with myelin antigen, and is associated with the modulation of CNS-infiltrating pDC phenotype and inhibition of CNS encephalitogenic T cells. This study may pave the way for novel pDC-based cell therapies in autoimmune diseases, aiming at specifically modulating pathogenic cells that induce and sustain autoimmune inflammation.
Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
Fernanda V
FV
Duraes
Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
Carla
C
Lippens
Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
Karin
K
Steinbach
Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
Juan
J
Dubrot
Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland.
Dale
D
Brighouse
Université Lyon 1, INSERM U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, LabEx DEVweCAN, Lyon, France.
Nathalie
N
Bendriss-Vermare
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Shohreh
S
Issazadeh-Navikas
Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland; Department of Pathology and Immunology, Division of Clinical Pathology, University & University Hospital of Geneva, Switzerland.
Doron
D
Merkler
Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland. Electronic address: Stephanie.hugues@unige.ch.
Stephanie
S
Hugues
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D064987:Cell- and Tissue-Based Therapy; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000276:immunology; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D001324:Autoantigens; C486456:CMKLR1 protein, mouse; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse
Cell therapy; Central nervous system; Experimental autoimmune encephalomyelitis; Plasmacytoid dendritic cells